MXPA06001099A - 2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases - Google Patents

Abstract

The present invention provides methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds, as well as methods of treating, preventing or ameliorating symptoms associated with such diseases. Specific examples of autoimmune diseases that can be treated or prevented with the compounds include rheumatoid arthritis and/or its associated symptoms, systemic lups erythematosis and/or its associated symptoms and multiple sclerosis and/or its associated symptoms.

Description

METHODS OF TREATMENT OR PREVENTION OF AUTOIMMUNE DISEASES WITH 2, 4-PYRIMIDINDIAMINE COMPOUNDS FIELD OF THE INVENTION The present invention relates generally to 2,4-pyrimidinediamine compounds, pharmaceutical compositions comprising the compounds, intermediates and synthetic methods for making the compounds and methods for using the compounds and compositions in a variety of contexts, such as as in the treatment or prevention of autoimmune diseases and / or the associated symptoms together with these.

BACKGROUND OF THE INVENTION The cross-linking of Fc receptors, such as the high affinity receptor for IgE (FceRI) and / or the high affinity receptor for IgG (Fc? RI), activates a signaling cascade in mast, basophilic and other cells. Immunities that result in the release of chemical mediators responsible for numerous adverse events. For example, such crosslinking leads to the release of preformed mediators of anaphylactic Type I (immediate) hypersensitivity reactions, such as histamine, from granulated storage sites via degranulation. It also leads to the synthesis and release of other mediators, including leukotrienes, prostaglandins and platelet activation factors (PAFs), which play important roles in inflammatory reactions. Additional mediators that are synthesized and released after crosslinking Fc receptors include cytokines and nitric oxide. The signaling cascade (s) activated by crosslinking of Fc receptors such as FceRI and / or Fc? RI comprises an array of cellular proteins. Among the most important intracellular signal propagators are tyrosine kinases. And, an important tyrosine kinase involved in the signal transduction pathways associated with the cross-linking of the FceRI and / or Fc? RI receptors, as well as with other cascades of signal transduction is the Syk kinase (see Valent et al., 2002, Intl. J. Hema tol. 75 (4): 257-362 for review). As the mediators released as a result of the cross-linking of the FceRI receptor and Fc? RI are responsible for, or play important roles in, the manifestation of numerous adverse events, the availability of compounds capable of inhibiting the cascade (s) of Signaling responsible for their release could be highly desirable. However, due to the critical role that the Syk kinase plays, these and other receptors of the signaling cascade (s), the availability of compounds capable of inhibiting the Syk kinase could be highly desirable.

SUMMARY OF THE INVENTION In one aspect, the present invention provides novel 2,4-pyrimidinediamine compounds which, as will be discussed in more detail below, have innumerable biological activities. The compounds generally comprise a 2,4-pyrimidinediamine "core" having the following structure and numbering convention: The compounds of the invention are substituted at the nitrogen C2 (N2) to form a secondary amine and are optionally further substituted at one or more of the following positions: nitrogen C4 (N4), position C5 and / or position C6. When substituted in N4, the substituent forms a secondary amine. The substituent on N2, as well as optional substituents at the other positions, can vary widely in physicochemical characteristics and characters. For example, the substituents may be a straight chain, or branched, or cyclic alkyl, a straight or branched or cyclic chain heteroalkyl, a mono or polycyclic aryl, a mono or polycyclic heteroaryl or combinations of these groups. These substituent groups may also be substituted, as will be described in more detail below. The substituents N2 and / or N4 may be attached directly to their respective nitrogen atoms, or they may be spaced apart from their respective nitrogen atoms via linkers, which may be the same or different. The nature of the linkers can vary widely, and can include virtually any combination of atoms or groups of atoms useful for spacing one molecular portion from another. For example, the linker can be an acyclic hydrocarbon bridge (eg, a saturated or unsaturated alkylene such as methane, ethane, ethene, propane, pro [1] ene, butane, but [1] ene, but [2] ene , buta [1,3] diene and the like), a monocyclic or polycyclic hydrocarbon bridge (eg, [1,2] benzene, [2, 3] naphthalene and the like), a heteroaryonic bridge or simple acyclic heteroalkyldiyl ( Example, -0-, -S-, -S-0-, -NH-, -PH-, -C (0) -, -C (0) NH-, -S (0) -, -S (0 ) 2-, -S (0) NH-, -S (0) 2NH-, -O-CH2-, -CH2-0-CH2-, -0-CH = CH-CH2- and the like), a heteroaryl bridge monocyclic or polycyclic (eg, [3,] furan, pyridino, thiophene, piperidino, piperazino, pyrazidino, pyrrolidino and the like) or combinations of such bridges. The substituent at the positions N2, N4, C5 and / or Cß, as well as the optional linkers, can also be substituted with one or more of the same or different substituent groups. The nature of these substituent groups can vary widely. Non-limiting examples of suitable substituent groups include mono or polycyclic aryls, straight or branched or cyclic chain alkyls, straight or branched or cyclic straight heteroalkyls, mono or polycyclic heteroaryls, haloes, straight or branched chain haloalkyls or cyclic, hydroxyl, oxo , thioxes, cyclic or straight chain or branched alkoxies, straight or branched chain haloalkoxy or cyclic, trifluoromethoxys, mono or polycyclic aryloxys, monocyclic or polycyclic heteroaryloxy, ethers, alcohols, sulphides, thioethers, sulfañil (thiols), imines, azos, azides, amines (primary, secondary and tertiary), nitriles (any isomer), cyanates (any isomer), thiocyanates (any isomer), nitroses, nitros, diazo, sulphoxides, sulphonyl, sulphonic acids, sulfonamides, sulfonamides, sulfamic esters, aldehydes, ketones, carboxylic acids, esters, amides, amidines, formadins, amino acids, acetylenes, carbamates, lactones, lactams, glucosides, glucuronides, sulfones, ketals, acetals, thiocetals, oximes, oxamic acids, oxamic esters, etc., and combinations of these groups. Substituent groups carrying reactive functionalities can be protected or deprotected, as is well known in the art. In an illustrative embodiment, the 2,4-pyrimidinediamine compounds of the invention are compounds according to structural formula (I): which include salts, hydrates, solvates and N-oxides thereof, wherein: L1 and L2 are each, independently from each other, selected from the group consisting of a direct link and a linker; R2 and R4 are described infra; R5 are selected from the group consisting of R6, alkyl (Cl-Cß) optionally substituted with one or more of the same or different R8 groups, (C1-C4) alkanyl optionally substituted with one or more of the same or different R8 groups, (C2-C4) alkenyl optionally substituted with one or more of the same or different R8 groups and (C2-C4) alkynyl optionally substituted with one or more of the same or different R8 groups; each R6 is independently selected from the group consisting of hydrogen, an electronegative group, -ORd, -SRd, haloalkyloxy (C1-C3), perhaloalkyloxy (C1-C3), -NRCRC, halogen, haloalkyl (C1-C3), perhaloalkyl (C1-C3), -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, -N3, - S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc, -S (0) 2NRcRc, -OS (0) Rd, -0S (02) Rd, -0S (0) 20Rd, -OS (0) NRcRc, -0S (0) 2NRcRc, -C (0) Rd, -C (0) ORd, -C (0) NRcRc, -C (NH) NRCRC, -OC ( 0) Rd, -SC (0) Rd, -0C (0) 0Rd, -SC (0) ORd, -OC (0) NRcRc, -SC (0) NRcRc, -OC (NH) NRCRC, -SC (NH) ) NRCRC, - [NHC (O)] pR, - [NHC (O)] nORd, - [NHC (O)] nNRcRc and - [NHC (NH)] nNRcRc, aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, arylalkyl (C6-C16) optionally substituted with one or more of the same or different R8 groups, 5-10 membered heteroaryl optionally substituted with one or more of the same or different R8 groups and heteroarylalkyl of 6-16 elements optionally substituted with one or more of the same or different R8 groups; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different groups Ra or Rb, -ORa substituted with one or more of the same or different Ra or R, -B (ORa) 2, -B (NRCRC) 2, - (CH ^ -R15, - (CHRa) i7¡-Rb, -0- (CH2) m -Rb, -S- (CH2) m ~ Rh, 0-CHRaR, -0-CRa (Rb) 2, -0- (CHRa ) ffl-Rb -O-ICH ^ -CHHCH ^ R ^ R13, -S- (CHRa) m -Rb, -C (0) NH- CH2) mR- ° r -C (0) NH- (CHRa) ffl -Rb, -O- (CH2) ^ -C (O) NH- (CH2) ffl-Rb, -S- (CH2) ^ -C (O) NH- (CH2) m -Rb, -O- (CHRa) m-C (O) NH- (CHRa) m -Rb, -S- (CHRa) ffl-C (0) NH- (CHRa) jp-Rb, -NH- (CH 2) ffl-Rb, -NH- (CHRa) m -Rb, -NH [(CH 2) mRb], - -NH-C (O) -NH- (CH2) ffl-Rb, -NH-C (O) - (CH2)? ¡-CHRbRb and -NH- (CH2) ffl-C (O) -NH- ( CH2) ffl-Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -ORd, haloalkyloxy (C1-C3), -OCF3, = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N0, = N2, -N3, -S (0) R, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc , -S (0) 2NRcRc, -0S (0) Rd, -0S (0) 2Rd, -0S (0) 20Rd, -OS (0) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) R, -C (NOH) NRcRc, -OC (0) Rd, -0C (0) 0Rd, - 0C (0) NRcRc; 0C (NH) NRcRc, -0C (NRa) NRcRc, ~ [NHC (0)] nRd, - [NRaC (O)] nRd, - [NHC (0)] nORá, - [NRaC (0)] n0Rd, - [NHC (0)] pNRcRc, - [NRaC (0)]? NRCRC, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently a protective group or Ra, alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which it may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently a protective group or Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3. In one embodiment, R5 is F and R6 is hydrogen. In another aspect, the present invention provides prodrugs of the 2,4-pyrimidinediamine compounds. Such prodrugs may be active in their prodrug form, or may be inactive until converted under physiological or other conditions of use, to an active drug form. In the prodrugs of the invention, one or more functional groups of the 2,4-pyrimidinediamine compounds are included in proportions that are cleaved from the molecule under conditions of use, typically by means of hydrolysis, enzymatic cleavage or some other unfolding mechanism, to provide the functional groups. For example, amino, primary or secondary groups can be included in an amide proportion that is split under conditions of use to generate the primary or secondary amino group. Thus, the prodrugs of the invention include special types of protecting groups, called "prodrugs", by masking one or more functional groups of the 2,4-pyrimidinediamine compounds that are split under the conditions of use to provide a drug compound of Active 2,4-pyrimidindiamine. Functional groups within the 2,4-pyrimidinediamine compounds that can be masked with progroups for inclusion in a proportion include, but are not limited to, amines (primary and secondary), hydroxyls, sulfanyls (thiols), carboxyls, carbonyls, phenols , catechols, diols, alkynes, phosphates, etc. Innumerable progroups suitable for masking such functional groups to provide proportions that can be cleaved under the desired conditions of use are known in the art. All these progroups, alone or in combinations, can be included in the prodrugs of the invention. Specific examples of proportions that provide primary or secondary amine groups, which may be included in the prodrugs of the invention include, but are not limited to, amides, carbamates, imines, ureas, phosphophenyls, phosphoryls and sulfenyls. Specific examples of proportions that give sulfanyl groups that can be included in the prodrugs of the invention include, but are not limited to, thioethers, e.g., S-methyl derivatives (monothio, dithio, oxythio, aminothio), thioether silyl, thioesters, thiocarbonates, thiocarbamates, asymmetric disulfides, etc. Specific examples of proportions that are split to give the hydroxyl groups that can be included in the prodrugs of the invention include, but are not limited to, sulfonates, esters and carbonates. Specific examples of proportions giving carboxyl groups that may be included in the prodrugs of the invention include, but are not limited to, esters (including silyl esters, oxamic acid esters and thioesters), amides and hydrazides. In an illustrative embodiment, the prodrugs of the invention are compounds according to structural formula (I), in which the protecting group of Rc and Rd is a progroup. In another illustrative embodiment, the prodrugs of the invention are compounds according to structural formula (II): which include salts, hydrates, solvates and N-oxides thereof, whe: R2, R4, R5, R6, L1 and L2 are as previously defined by the structural formula (I); R2b is a progroup; R4b is a progroup or an alkyl group, for example, methyl, and as further defined by the examples. In another aspect, the present invention provides compositions comprising one or more compounds and / or prodrugs of the invention and a suitable carrier, excipient or diluent. The exact nature of the carrier, excipient or diluent will depend on the intended use for the composition and can range from being suitable or acceptable for veterinary use to being suitable or acceptable for human use. In yet another aspect, the present invention provides intermediates useful for synthesizing the 2,4-pyrimidinediamine compounds and prodrugs of the invention. In one embodiment, the intermediates are 4-pyrimidinamines according to structural formula (III): which includes salts, hydrates, solvates and N-oxides thereof, wherein R4, R5, Rd and L2 are as previously defined by the structural formula (I); LG is a leaving group such as, for example, S (0) 2Me, -SMe or halo (eg, F, Cl, Br, I); and R 4c is hydrogen, a progroup, an alkyl group or as described herein.

In another embodiment, the intermediates are 2-pyrimidinediamines according to structural formula (IV): which includes salts, hydrates, solvates and N-oxides thereof, wherein R2, R5, R6 and L1 are as previously defined by the structural formula (I); LG is a leaving group, such as, for example, -S (0) 2Me, -SMe or halo (eg, F, Cl, Br, I) and. In yet another embodiment, the intermediates are 4-a ino or 4-hydroxy-2-pyrimidinamines in accordance with structural formula (V): which includes salts, hydrates, solvates and N-oxides thereof, wherein R2, R5, R6 and L1 are as previously defined by the structural formula (I), R7 is an amino or hydroxyl group and R2c is hydrogen or a progroup . In another embodiment, the intermediates are substituted N-4 cytokines in accordance with structural formula (VI): which includes salts, hydrates, solvates and N-oxides thereof, wherein R4, R5, R6 and L2 are as previously defined by the structural formula (I) and R4c ~ is as previously defined in the formula (III). In yet another aspect, the present invention provides methods for synthesizing the 2,4-pyrimidinediamine compounds and prodrugs of the invention. In one embodiment, the method involves reacting a 4-pyrimidinamine according to structural formula (III) with an amine of the formula HR2cN-L1-R2, wherein L1, R2 and R2c are as previously defined by the structural formula (IV) to provide a 2,4-pyrimididiamine in accordance with structural formula (I) or a prodrug in accordance with structural formula (II). In another embodiment, the method involves reacting a 2-pyrimidinamine according to structural formula (IV) with an amine of formula R-L2-NHRc, wherein L4, R4 and Rc are as previously defined by the structural formula ( III) to provide a 2,4-pyrimidinediamine according to the structural formula (I) or a prodrug in accordance with the structural formula (II) • In yet another embodiment, the method involves reacting a 4-amino-2-pyrimidinamine according to the structural formula (V) (in which R7 is an amino group) with an amine of the formula R4-L4 -NHR4c, wherein L2, R4 and R4c are as defined for structural formula (III), to give a 2,4-pyrimidinediamine in accordance with structural formula (I) or a prodrug in accordance with structural formula (II) ). Alternatively, the 4-amino-2-pyrimidinamine can be reacted with a compound of the formula R-L2-LG, wherein R4 and L2 are as previously defined for the structural formula (I) and LG is a leaving group. In still another embodiment, the method involves halogenating a 4-hydroxy-2-pyrimidinamine in accordance with structural formula (V) (R7 is a hydroxyl group) to give a 2-pyrimidinamine in accordance with structural formula (IV) and reacting this pyrimidinamine with an appropriate amine, as described above. In yet another embodiment, the method involves halogenating a N4-substituted cytokine in accordance with structural formula (VI) to give a 4-pyrimidinamine according to structural formula (II) and reacting this pyrimidinamine with an appropriate amine, as described above. The 2,4-pyrimidinediamine compounds of the invention are potent inhibitors of the degranulation of immune cells, such as mast cells, basophils, neutrophils and / or eosinophils. Thus, in yet another aspect, the present invention provides methods for regulating, and in particular, inhibiting the degranulation of such cells. The method generally involves contacting a cell that is degranulated with an amount of a compound 2., 4-pyrimidinediamine or prodrug of the invention, or a salt, hydrate, solvate, N-oxide and / or composition thereof, acceptable, effective to regulate or inhibit degranulation of the cell. The method can be practiced in in vitro contexts or in in vivo contexts, as a therapeutic procedure towards the treatment or prevention of diseases, characterized by, caused by or dissociated with cellular degranulation. While not intended to be bound by any theory of operation, the biochemical data confirm that the 2,4-pyrimidinediamine compounds exert their inhibitory effect on degranulation, at least in part, by blocking or inhibiting the transduction cascade (s) of signal by cross-linking the high affinity Fc receptors for IgE ("FceRI") and / or IgG ("Fc? RI"). However, the 2,4-pyrimidinediamine compounds are potent inhibitors of both FceRI mediated and Fc? RI mediated degranulation. As a consequence, the 2,4-pyrimidine compounds can be used to inhibit these Fc receptor signaling cascades in any of the cell types that express such FceRI and / or Fc? RI receptors, including but not limited to, macrophage cells, mast, basophils, neutrophils and / or eosinophils. The methods also allow the regulation of, and in particular, the inhibition of, downstream processes that result as a consequence of activation of such signaling cascade (s) of the Fc receptor. Such a downstream process includes, but is not limited to, degranulation mediated by both FceRI and / or mediated by Fc? RI, cytokine production and / or production and / or release of lipid mediators such as leukotrienes and prostaglandins. The method generally involves contacting a cell expressing an Fc receptor, such as one of the types discussed above, with an amount of a 2,4-pyrimidinediamine compound or prodrug of the invention, or a salt, hydrate, solvent, N-oxide and / or acceptable composition thereof, effective to regulate or inhibit the signaling cascade of the Fc receptor and / or a downstream process effected by the activation of this signaling cascade. The method can be practiced in in vitro contexts or in in vivo contexts as a therapeutic procedure towards the treatment or prevention of diseases characterized by, caused by or associated with the Fc receptor signaling cascade, such as diseases effected by the release of mediators. specific granule chemicals, after degranulation, cytokine release and / or synthesis and / or release and / or synthesis of lipid mediators such as leukotrienes and prostaglandins. In still another aspect, the present invention provides methods for treating and / or preventing diseases, characterized by, caused by or associated with the release of chemical mediators as a consequence of activation of signaling cascades of the Fc receptor, such as signaling cascades. of FceRI and / or Fc? RI. The methods can be practiced on animals in a veterinary context or in humans. The methods generally involve administering to an animal or human subject, an amount of a 2,4-pyrimidinediamine compound or prodrug of the invention, or a salt, hydrate, solvate, N-oxide and / or acceptable, effective composition thereof. to treat or prevent the disease. As discussed previously, activation of the FceRI or FcRI receptor signaling cascade in certain immune cells leads to the release and / or synthesis of a variety of chemicals that are pharmacological mediators of a wide variety of diseases. Any of these diseases can be treated or prevented in accordance with the methods of the invention. For example, in mast cells and basophilic cells, activation of the FceRI or Fc? RI signaling cascade leads to immediate release (ie, within 1-3 minutes of receptor activation), of preformed mediators of atopic and / or Type I hypersensitivity reactions (for example, histamine, proteases such as tripase, etc.) via the degranulation process. Such atopic or Type I hypersensitivity reactions, include, but are not limited to, anaphylactic reactions to the environment and other allergens (e.g., pollen, insect and / or animal venoms, foods, drugs, contrast dyes, etc.), anaphylactoid reactions, hay fever, allergic conjunctivitis, allergic rhinitis, allergic asthma, atopic dermatitis, eczema, urticaria, mucosal disorders, tissue disorders and certain gastrointestinal disorders. The immediate release of the preformed mediators via degranulation is followed by the release and / or synthesis of a variety of other chemical mediators, including, among other things, platelet activation factor (PAF), prostaglandins and leukotrienes (e.g., LTC4). ) and de novo synthesis and release of cytokines such as TNFa, IL-4, IL-5, IL-6, IL-13, etc. The first of these two processes occurs approximately 3-30 minutes after receptor activation; the last approximately 30 minutes-7 hours after the activation of the receiver. These "late stage" mediators are thought to be partly responsible for the chronic symptoms of the atopic and Type I hypersensitivity reactions listed above, and in addition, are chemical mediators of inflammation and inflammatory diseases (eg, osteoarthritis, disease inflammatory bowel, ulcerative colitis, Crohn's disease, inflammatory idiopathic bowel disease, irritable bowel syndrome, spastic colon, etc.), low-grade scars (eg, scleroderma, increased fibrosis, keloids, post-surgical scars, fibrosis pulmonary, vascular spasms, migraine, reperfusion injury and post-myocardial infarction) and complex or dryness syndrome. All of these diseases can be treated or prevented in accordance with the methods of the invention. Additional diseases which can be treated or prevented in accordance with the methods of the invention include diseases associated with the pathology of basophilic cells and / or mast cells. Examples of such diseases include, but are not limited to, skin diseases such as scleroderma, heart diseases such as post-myocardial infarction, lung diseases such as pulmonary muscle changes or remodeling and chronic obstructive pulmonary diseases (COPD) and diseases of the lung. intestine such as inflammatory bowel syndrome (spastic colon). The 2,4-pyrimidinediamine compounds of the invention are also potent inhibitors of the Syk kinase of tyrosine kinase. Thus, in still another aspect, the present invention provides methods for regulating and in particular, inhibiting the activity of the Syk kinase. The method generally involves contacting a Syk kinase or a cell comprising a kinase with an amount of a 2,4-pyrimidinediamine compound or prodrug of the invention, or a salt, hydrate, solvate, N-oxide of the invention. same and / or acceptable composition thereof, effective to regulate or inhibit the activity of Syk kinase. In one embodiment, the Syk kinase is an isolated or recombinant Syk kinase. In another embodiment, the Syk kinase is an endogenous or recombinant Syk kinase expressed by a cell, for example, a mast cell or a basophil cell. The method can be practiced in in vitro contexts or in in vivo contexts, as a therapeutic procedure towards the treatment or prevention of diseases, characterized by, caused by, or associated with the activity of Syk kinase. While not intended to be bound by any particular theory of operation, it is believed that the 2,4-pyrimidinediamine compounds of the invention inhibit cellular degranulation and / or the release of other chemical mediators primarily by inhibiting the Syk kinase that becomes activated through of the FceRI range chain homodimer (see, for example, Figure 2). This gamma-chain homodimer is carried by other Fc receptors, including Fc? RI, Fc? RIII and FcaRI. For all these receptors, transduction of the intracellular signal is mediated by the common gamma-chain homodimer. The binding and aggregation of these receptors results in the recruitment and activation of tyrosine kinases such as Syk kinase. As a consequence of these common signaling activities, the 2,4-pyrimidinediamine compounds described herein can be used to regulate, and in particular, inhibit signaling cascades of Fc receptors having this gamma-chain homodimer, such as FceRI, Fc? RI, Fc? RIII and FcaRI, as well as the cellular responses elicited through these receptors. The kinase is known to play a critical role in other signaling cascades. For example, Syk kinase is an effector of B-cell receptor signaling (BCR) (Turner et al., 2000, Immunology Today 21: 148-154) and is an essential component of beta-integrin signaling (l), beta (2) and beta (3) in neutrophils (Mocsai et al., 2002, Immunity 16: 547-558). As the 2,4-pyrimidinediamine compounds described herein are potent inhibitors of the Syk kinase, they can also be used to regulate, and in particular, inhibit any signaling cascade wherein Syk plays a role, such as, for example, the Fc receptor, BCR and integrin signaling cascades, as well as the cellular responses elicited through these signaling cascades. The particular cellular response regulated or inhibited will depend, in part, on the specific cell type and receptor signaling cascade, as is well known in the art. Non-limiting examples of cellular responses that can be regulated or inhibited with the 2,4-pyrimidinediamine compounds include a respiratory burst, cell adhesion, cellular degranulation, cellular distribution, cell migration, phagocytosis (e.g., in macrophages), ion flux calcium (for example, in mast, basophilic, neutrophilic, eosinophilic and B cells), platelet aggregation and cell maturation (for example, in B cells). Thus, in another aspect, the present invention provides methods for regulating, and in particular, inhibiting signal transduction cascades in which Syk plays a role. The method generally involves contacting a Syk-dependent receptor or a cell expressing a Syk-dependent receptor with an amount of a 2,4-pyrimidinediamine compound or prodrug of the invention, or a salt, hydrate, solvate, N-oxide and / or acceptable composition thereof, effective to regulate or inhibit the signal transduction cascade. The methods can also be used to regulate, and in particular, inhibit downstream processes or cellular responses caused by the activation of the particular Syk-dependent signal transduction cascade. The methods can be practiced to regulate in any cascade of signal transduction, where the Syk is not known or discovered later by playing a role. The methods may be practiced in in vitro contexts or in in vivo contexts as a therapeutic procedure towards the treatment or prevention of diseases, characterized by, or caused by, or associated with the activation of the Syk-dependent signal transduction cascade. Non-limiting examples of such diseases include those previously discussed. The cellular and animal data also confirm that the 2,4-pyrimidinediamine compounds of the invention can also be used to treat or prevent autoimmune diseases and / or symptoms of such diseases. The methods generally involve administering to a subject suffering from an autoimmune disease or at risk of developing an autoimmune disease, an amount of a 2,4-pyrimidinediamine of the method or prodrug of the invention, or a salt, N-oxide , hydrate, solvate or composition thereof, effective to treat or prevent the autoimmune disease and / or its associated symptoms. Autoimmune diseases that can be treated or prevented with the 2,4-pyrimidinediamine compounds include those diseases that are commonly associated with non-anaphylactic hypersensitivity reactions (Type II, Type III and / or Type IV hypersensitivity reactions) and / or those diseases that are mediated, at least in part, by the activation of the FcγR signaling cascade in monocyte cells. Such autoimmune diseases include, but are not limited to, those autoimmune diseases that are frequently referred to as single organ or single cell type autoimmune disorders and those autoimmune diseases that are frequently designated to involve systemic autoimmune disorders. Non-limiting examples of diseases frequently referred to as single organ or single cell type autoimmune disorders include: Hashimoto's thyroiditis, autoimmune hemolytic anemia, atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, good Shepherd's disease, autoimmune thrombocytopenia, sympathetic ophthalmia, myasthenia gravis, Graves' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy. Non-limiting examples of diseases often designated to involve systemic autoimmune disorders include: systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis, and pemphigoid bolus.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 provides a drawing illustrating the production induced by allergens of IgE and consequent release of preformed chemical mediators and others from mast cells; Figure 2 provides a drawing illustrating the FceRI signal transduction cascade leading to the degranulation of mast and / or basophil cells; and Figure 3 provides a drawing illustrating the putative action points of compounds that selectively inhibit FceRI-mediated degranulation and compounds that inhibit both mediated degranulation.

FceRI as induced by ionomycin.

DETAILED DESCRIPTION OF THE INVENTION Definitions As used herein, the following terms are proposed to have the following meanings: "Alkyl" by itself or as part of another substituent, refers to a cyclic or straight-chain, branched, saturated or unsaturated monovalent hydrocarbon radical which has the declared number of carbon atoms (ie, C1-C6 means from one to six carbon atoms), which is derived by the removal of a hydrogen atom from a single carbon atom of an alkane, alkene or original alkyne. Typical alkyl groups include, but are not limited to, methyl; ethyl esters such as ethanyl, ethenyl, ethynyl; propyl such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl cycloprop-1-en-1-yl; cycloprop-2-en-l-yl, prop-1-yn-l-yl, prop-2-yn-l-yl, etc .; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-1-yl , but-l-en-2-yl, 2-methyl-prop-1-en-l-yl, but-2-en-yl, but-2-en-2-yl, buta-1,3-dien -1-yl, buta-1, 3-dien-2-yl, cyclobut-1-en-l-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-l-yl, but -1-in-l-yl, but-l-in-3-yl, but-3-yn-l-yl, etc .; and similar. Where specific levels of saturation are proposed, the nomenclature "alkanyl", "alkenyl" and / or "alkynyl" is used, as defined below. In preferred embodiments, the alkyl groups are (C1-C6) alkyl. "Alkanyl" by itself, or as part of another substituent, refers to a saturated straight or branched chain cyclic alkyl, derived by the removal of a hydrogen atom from a single carbon atom of an original alkane. Typical alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl (isopropyl), cyclopropan-1-yl, etc .; butanyls such as butan-1-yl, butan-2-yl (sec-butyl), 2-methyl-propan-1-yl (isobutyl), 2-methyl-propan-2-yl (t-butyl), cyclobutan- 1-ilo, etc .; and similar. In preferred embodiments, the alkanyl groups are (C1-C6) alkanyl. "Alkenyl" by itself or as part of another substituent, refers to an unsaturated straight or branched chain, cyclic alkyl having at least one carbon-carbon double bond derived by the removal of a hydrogen atom from a single carbon atom of an original alkene. The group can be in either the cis or trans conformation around the double bond (s). Typical alkenyl groups include, but are not limited to, ethenyl; propenyls such as prope-1-en-l-yl, prop-l-en-2-yl, prop-2-en-l-yl, prop-2-en-2-yl, cycloprop-1-en-l -ilo; cycloprop-2-en-l-yl; butenyls such as but-1-en-l-yl, but-l-en-2-yl, 2-methyl-prop-1-en-l-yl, but-2-en-l-yl, but-2 -in-2-yl, buta-1, 3-dien-l-yl, buta-1,3-dien-2-yl, cyclobut-1-en-l-yl, cyclobut-l-en-3-yl , cyclobuta-1, 3-dien-1-yl, etc .; and similar. In preferred embodiments, the alkenyl group is (C2-C6) alkenyl. "Alkynyl" by itself or as part of another substituent, refers to an unsaturated branched, straight chain, cyclic alkyl having at least one carbon-carbon triple bond derived by the removal of a hydrogen atom from a single carbon atom of an original alkyne. Typical alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-l-in-1-yl, prop-2-yn-l-yl, etc .; butynyls such as but-l-in-1-yl, but-l-yn-3-yl, but-3-yn-l-yl, etc .; and similar. In preferred embodiments, the alkynyl group is (C2-C6) alkynyl. "Alkylidene" by itself or as part of another substituent, refers to a cyclic or straight chain, branched, saturated or unsaturated hydrocarbon group having the number of carbon atoms declared (ie, C1-C6 means one to six carbon atoms), derived by the removal of one hydrogen atom from each of the two different carbon atoms of an original alkane, alkene or alkyne, or by the removal of two hydrogen atoms from a single carbon atom of an original alkane, alkene or alkyne. The two monovalent radical centers or each valence of the center of the divalent radical can form bonds with the same or different atoms. Typical alkyldiyl groups, include but are not limited to methanediyl; etildyls such as ethan-1, 1-diyl, ethane-1,2-diyl, ethen-1,1-diyl, ethen-1,2-diyl; propyldiils such as propan-1,1-diyl, propan-1,2-diyl, propan-2,2-diyl, propan-1,3-diyl, cyclopropan-1,1-diyl, cyclopropan-1,2-diyl , prop-l-en-1, 1-diyl, prop-l-en-1,2-diyl, prop-2-en-1,2-diyl, prop-l-en-1,3-diyl, cyclopropyl -l-en-1, 2-diyl, cycloprop-2-en-l, 2-diyl, cycloprop-2-en-l, 1-diyl, propl-1-in-1,3-diyl, etc .; butyldyls such as, butan-1, 1-diyl, butan-1,2-diyl, butan-1,3-diyl, butan-1,4-diyl, butan-2,2-diyl, 2-methyl-propan- 1, 1-diyl, 2-methyl-propan-1, 2-diyl, cyclobutan-1, 1-diyl; Cyclobutan-1,2-diyl, cyclobutan-1,3-diyl, butan-1-en-1,1-diyl, but-1-en-1,2-diyl, but-1-en-1,3- diyl, but-l-en-1, 4-diyl, 2-methyl-prop-l-en-l, 1-diyl, 2-methanilidene-propan-l, 1-diyl, buta-1,3-dien- l, 1-diyl, buta-1,3-dien-l, 2-diyl, buta-1,3-dien-l, 3-diyl, buta-1,3-dien-1,4-diyl, cyclobutyl l-en-1, 2-diyl, cyclobut-l-en-1,3-diyl, cyclobut-2-en-l, 2-diyl, cyclobuta-1,3-dien-l, 2-diyl, cyclobuta- 1,3-dien-1, 3-diyl, but-l-lin-1,3-diyl, but-l-in-1,4-diyl, buta-1,3-diin-l, 4-diyl, etc.; and similar. Where specific levels of saturation are proposed, the nomenclature is used alkyldiyl, alkenyldiyl and / or alkynyldiyl. Where it is specifically intended that two valences be in the same carbon atom, the nomenclature "alkylidene" is used. In preferred embodiments, the alkyldiyl group is (C 1 -C 6) alkyldiyl. Also preferred are saturated acyclic alkyldiyl groups in which the radical centers are in the terminal carbons, for example, methanediyl (methane); ethane-1,2-diyl (ethane); propan-1,3-diyl (propane); butan-1, -diyl (butane); and similar (also referred to as alkyols, defined infra). "Alkylene" by itself or as part of another substituent, refers to a saturated straight or unsaturated alkyldiyl group, having two terminal monovalent radical centers derived by the removal of one hydrogen atom from each of the two terminal carbon atoms of straight chain alkane, alkene or alkyne. The location of a double bond or triple bond, if present, in a particular alkylene, is indicated in square brackets. Typical alkylene groups include, but are not limited to, methane; ethylenes such as ethane, ethene, ethyne; propylenes such as propane, prop [1] ene, propan [1, 2] diene, prop [1] ino, etc .; butylenes such as butane, but [1] ene, but [2] ene, buta [1, 3] diene, but [1] ino, but [2] ino, buta [1, 3] diino, etc .; and similar. Where specific levels of saturation are proposed, the nomenclature alkane, alkene and / or alkyne is used. In preferred embodiments, the alkylene group is (C1-C6) alkylene or (C1-C3) alkylene. Also preferred are straight-chain saturated alkane groups, for example, methane, ethane, propane, butane and the like. "Heteroalkyl", "Heteroalkanyl", "Heteroalkenyl", "Heteroalkynyl", "Heteroalkyldiyl" and "Heteroalkylene", by themselves, or as part of another substituent, refer to alkyl, alkanyl, alkenyl, alkynyl, alkyldiyl and alkylene groups, respectively, in which one or more than the carbon atoms are each independently, replaced with the same or different heteroatom groups or heteroatoms. Typical heteroatom and / or heteroatom groups which can be replaced with the carbon atoms include, but are not limited to, -O-, -S-, -S-0-, -NR'-, -PH-, - S (O) -, -S (0) 2-, -S (O) NR'-, -S (0) 2NR'-, and the like, which include combinations thereof, wherein each R 'is independently hydrogen or (C1-C6) alkyl. "Cycloalkyl" and "Heterocycloalkyl" by themselves or as part of another substituent, refer to cyclic versions of "alkyl" and "heteroalkyl" groups, respectively. By heteroalkyl groups, a heteroatom may occupy the position that is attached to the rest of the molecule. Typical cycloalkyl groups include, but are not limited to, cyclopropyl; cyclobutyls such as cyclobutanyl and cyclobutenyl; cyclopentyls such as cyclopentanyl and cyclopentenyl; cyclohexyl such as cyclohexanyl and cyclohexenyl; and similar. Typical heterocycloalkyl groups include, but are not limited to, tetrahydrofuranyl (e.g., tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, etc.), piperidinyl (e.g., piperidinium-1-yl, piperidin-2-yl, etc. .), morpholinyl (e.g., morpholin-3-yl, morpholin-4-yl, etc.), piperazinyl (e.g., piperazin-1-yl, piperazin-2-yl, etc.), and the like. "Acyclic Heteroaromatic Bridge" refers to a divalent bridge in which the atoms of the structure are exclusively heteroaromatic groups and / or heteroatoms. Typical acyclic heteroaromatic bridges include, but are not limited to, -O-, -S-, -SO-, -NR'-, -PH-, -S (O) -, -S (0) 2-, - S (O) NR'-, -S (0) 2NR'-, and the like, which include combinations thereof, wherein each R 'is independently hydrogen or (C1-C6) alkyl. "Original Aromatic Ring System" refers to an unsaturated cyclic or polycyclic ring system, which has a conjugated p-electron system. Specifically included with the definition of "original aromatic ring system", are fused ring systems, in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, fluorene , indane, indene, phenalene, tetrahydronaphthalene, etc. Typical original aromatic ring systems include, but are not limited to, aceanthylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronen, fluoranthene, fluorene, hexacene, hexane, hexalene, indacene, s-indacene, indane, indene , naphthalene, octazene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picenum, pleyadene, pyrene, pyrantrene, rubiceno, tetrahydronaphthalene, triphenylene, trinaphthalene and the like, as also the various hydroisoisomers thereof. "Aryl" by itself or as part of another substituent, refers to a monovalent aromatic hydrocarbon group having the number of carbon atoms declared (ie, C5-C15 means from 5 to 15 carbon atoms), derived by the Removal of a hydrogen atom from a single carbon atom of an original aromatic ring system. Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexane, hexalene, as-indacene, s-indacene, indane. , indene, naphthalene, octazene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picenum, pylene, pyrene, pyrantrene, rubiceno, tetrahydronaphthalene, triphenylene, trinaphthalene and the like , as well as the various hydroisoisomers thereof. In preferred modalities, the aryl group is aryl (C5-C15), with (C5-C10) being still more preferred. Particularly preferred aryls are cyclopentadienyl, phenyl and naphthyl. "Arylaryl by itself or as part of another substituent, refers to a monovalent hydrocarbon group derived by the removal of a hydrogen atom from a single carbon atom of a ring system in which, two or more systems of identical or non-identical original aromatic ring, are directly linked together by a single bond, where the number of such direct ring junctions are less than the number of original aromatic ring systems involved.The typical arylaryl groups include, but are not they limit a, biphenyl, triphenyl, phenyl-naphthyl, binaphthyl, biphenyl-naphthyl and the like .. Where the number of carbon atoms in an aryl group are specified, the numbers refer to the carbon atoms comprising each original aromatic ring. For example, arylaryl (C5-C15) is an aryl group in which, each aromatic ring comprises from 5 to 15 carbon atoms, for example, biphenyl, triphenyl, binaphthyl, phenylnaphthyl, etc. Preferably, each original aromatic ring system of an arylaryl group is independently an aromatic (C5-C15), more preferably an aromatic (C5-C10). Also preferred are arylaryl groups in which all the original aromatic ring systems are indicated, for example, biphenyl, triphenyl, binaphthyl, trinaphthyl, etc. "Biaryl" by itself or as part of another substituent, refers to an arylaryl group having two identical original aromatic systems directly linked together by a single bond. Typical biaryl groups include, but are not limited to, biphenyl, binaphthyl, biantracyl, and the like. Preferably, the aromatic ring systems are aromatic rings (C5-C15), more preferably aromatic rings (C5-C10). A particularly preferred biaryl group is biphenyl. "Arylalkyl" by itself or as part of another substituent, refers to an acyclic alkyl group in which, one of the hydrogen atoms attached to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an aryl group. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2-naphthyleten-1-yl, naphthobenzyl, 2-naptophenyletan-1-yl and the like. Where specific alkyl portions are proposed, the arylalkanyl, arylalkenyl and / or arylalkynyl nomenclature is used. In preferred embodiments, the arylalkyl group is arylalkyl (C6-C21), for example, the alkanyl, alkenyl or alkynyl portion of the arylalkyl group is (C1-C6) and the aryl portion is (C5-C15). In particularly preferred embodiments, the arylalkyl group is (C6-C13), for example, the alkanyl, alkenyl or alkynyl portion of the arylalkyl group is (C1-C3) and the aryl portion is (C5-C10). "Original Heteroaromatic Ring System", refers to an original aromatic ring system in which, one or more carbon atoms are each independently replaced with the same or different heteroatomic groups or heteroatoms. Typical heteroatom or heteroatom groups to replace the carbon atoms include, but are not limited to, N, NH, P, 0, S, S (0), S (0) 2, Si, etc. Specifically included within the definition of "original heteroaromatic ring systems", are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, benzodioxane , benzofuran, chroman, chromene, indole, indoline, xanthene, etc. Also included in the definition of "original heteroaromatic ring system" are those recognized rings that include such common substituents, such as, for example, benzopyrone and 1-methyl-1,2,3,4-tetrazole. Specifically excluded from the definition of "original heteroaromatic ring system" are benzene rings fused to cyclic polyalkylene glycols, such as cyclic polyethylene glycols. Systems typical original heteroaromatic ring include, but are not limited to, acridine, benzimidazole, benzisoxazole, benzodioxan, benzodioxole, benzofuran, benzopyrone, benzothiadiazole, benzothiazole, benzotriazole, benzoxaxina, benzoxazole, benzoxazoline, carbazole, bípicos include, but are not limited to, acridine, benzimidazole, benzisoxazole, benzodioxan, benzodioxole, benzofuran, benzopyrone, benzothiadiazole, benzothiazole, benzotriazole, benzoxaxina, benzoxazole, benzoxazoline, carbazole, beta-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, peri idina, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole , pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene and the like. "Heteroaryl" by itself or as part of another substituent, refers to a monovalent heteroaromatic group having the number of ring atoms declared (for example, "5-14 elements" means from 5 to 15 ring atoms) derived by the removal of a hydrogen atom from a single atom of an original heteroaromatic ring system. Typical heteroaryl groups include, but are not limited to, groups derived from acridine, benzimidazole, benzisoxazole, benzodioxan, benzodiaxol, benzofuran, benzopyrone, benzothiadiazole, benzothiazole, benzotriazole, benzoxazine, benzoxazole, benzoxazoline, carbazole, beta-carboline, chromane, chromene , cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran , pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like, as well as various hydro isomers thereof. In preferred embodiments, the heteroaryl group is a heteroaryl of 5-14 elements, with heteroaryl of 5-10 elements being particularly preferred. "Heteroaryl-Heteroaryl" by itself or as part of another substituent, refers to a monovalent heteroaromatic group derived by the removal of a hydrogen atom from a single atom of a ring system in which, two or more systems of identical or non-identical original heteroaromatic ring, are directly linked together by a single bond, wherein the number of such direct ring junctions is less than the number of original heteroaromatic ring systems involved. Typical heteroaryl heteroaryl groups include, but are not limited to, bipyridyl, tripyridyl, pyridylpurinyl, bipininyl, etc. Where the number of atoms is specified, the numbers refer to the number of atoms that comprise each original heteroaromatic ring system. For example, heteroaryl-heteroaryl of 5-15 elements is a heteroaryl-heteroaryl group in which, each original heteroaromatic ring system comprises from 5 to 15 atoms, for example, bipyridyl, tripyridyl, etc. Preferably, each original heteroaromatic ring system is independently, a heteroaromatic of 5-15 elements, more preferably a heteroaromatic of 5-10 elements. Also preferred are heteroaryl heteroaryl groups in which all the original heteroaromatic ring systems are identical. "Biheteroaryl" by itself or as part of another substituent, refers to a heteroaryl heteroaryl group having two identical original heteroaromatic ring systems, directly linked together by a single bond. Typical biheteroaryl groups include, but are not limited to, bipyridyl, bipyrinyl, biquinolinyl and the like. Preferably, heteroaromatic ring systems are heteroaromatic rings of 5-15 elements, more preferably heteroaromatic rings of 5-10 elements. "Heteroarylalkyl" by itself or as part of another substituent, refers to an acyclic alkyl group in which, one of the hydrogen atoms attached to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an heteroaryl group. Where specific alkyl portions are proposed, the heteroarylalkane, heteroarylalkenyl and / or heteroarylalkynyl nomenclature is used. In preferred embodiments, the heteroarylalkyl group is a heteroarylalkyl of 6-21 elements, for example, the alkanyl, alkenyl or alkynyl portion of the heteroarylalkyl is (C1-C6) alkyl and the heteroaryl portion is a heteroaryl of 5-15 elements. In particular preferred embodiments, the heteroarylalkyl is a heteroarylalkyl of 6-13 elements, for example, the alkanyl, alkenyl or alkynyl portion is (C1-C3) alkyl, and the heteroaryl portion is a 5-10-membered heteroaryl. "Halogen" or "Halo" by itself or as part of another substituent, unless otherwise stated, refers to fluoro, chloro, bromo and iodo. "Haloalkyl" by itself or as part of another substituent, refers to an alkyl group in which one or more of the hydrogen atoms is replaced with a halogen. Thus, the term "haloalkyl" means to include monohaloalkyls, dihaloalkyls, trihaloalkyls, etc., up to perhaloalkyls. For example, the term "(C1-C2) haloalkyl" includes trifluoromethyl, dilfuoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 1,2-difluoroethyl, 1,1-trifluoroethyl, perfluoroethyl, etc. The groups defined above may include prefixes and / or suffixes that are commonly used in the art to create additional well-known substituent groups. As examples, "alkyloxy" or "alkoxy" refers to a group of the formula -OR "," alkylamine "refers to a group of the formula -NHR" and "dialkylamine" refers to a group of the formula - NR "R", wherein each R "is independently an alkyl As another example," haloalkoxy "or" haloalkyloxy "refers to a group of the formula -OR '' ', wherein R' '' is a haloalkyl. "Protective group" refers to a group of atoms that, when bound to a reactive functional group in a molecule, mask, reduce or prevent the reactivity of the functional group Typically, a protecting group can be selectively removed as desired during the course of a synthesis Examples of protecting groups can be found in Greene and Wuts, Protective Groups in Organic Chemistry, 3rd Ed., 1999, John Wiley &; Sons, NY and Harrison et al. , Compendium of Synthetic Organic Methods, Vols. 1-8, 1971-1996, John Wiley & Sons, NY. Preferred amino protecting groups include, but are not limited to, formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl ("CBZ"), tert-butoxycarbonyl ("Boc"), trimethylsilyl ("TMS"), 2-trimethylsilyl-ethanesulfonyl (" TES "), trifyl and substituted trifyl groups, alkoxycarbonyl, 9-fluorenylmethyloxycarbonyl (" FMOC "), nitro-veratryloxycarbonyl (" NVOC ") and the like. Representative hydroxyl protecting groups include, but are not limited to, those in which the hydroxyl group is either acylated or alkylated, such as benzyl and trifly ethers, as well as also alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers (e.g. , TMS or TIPPS groups) and allyl ethers. "Prodrug" refers to a derivative of an active 2,4-pyrimidinediamine compound (drug), which requires a transformation under the conditions of use, such as within the body, to release the active 2,4-pyrimidinediamine drug. Prodrugs are frequently, but not necessarily, pharmacologically inactive until they become the active drug. Prodrugs are typically obtained by masking a functional group in the 2,4-pyridinediamine drug which is believed to be in part required by its activity with a progroup (defined below), to form a proportion which undergoes a transformation, such as cleavage , under the specified conditions of use to release the functional group, and therefore, the active 2, 4-pyrimidinediamine drug. The splitting of the ratio can proceed spontaneously, such as by means of a hydrolysis reaction, or it can be catalyzed or induced by another agent, such as by an enzyme, by light, by acid or base, or by a change of or exposure to an environmental or physical parameter, such as a change in temperature. The agent can be endogenous to the conditions of use, such as an enzyme present in the cells to which the prodrug is administered, or to the acidic conditions of the stomach, or it can be exogenously supplied. A wide variety of progroups, as well as the resulting proportions, suitable for masking functional groups in the active 2-pyrimidinediamine compounds to give prodrugs, are well known in the art. For example, a hydroxy functional group can be masked as a sulfonate, ester or carbonate ratio, which can be hydrolyzed in vivo to provide the hydroxyl group. An amino functional group can be masked as an amide, carbamate, imine, urea, phosphenyl, phosphoryl or sulfenyl proportion, which can be hydrolyzed in vivo to provide the amino group. A carboxyl group can be masked as an ester ratio (which includes silyl esters and thioesters), amide or hydrazide, which can be hydrolyzed in vivo to provide the carboxyl group. The nitrogen protecting groups and nitrogen pro-drugs of the invention may include lower alkyl groups, as well as amides, carbamates, etc. Other specific examples of suitable progroups and their respective proportions will be apparent to those skilled in the art. "Prodrug" refers to a type of protecting group that, when used to mask a functional group within an active 2, 4-pyrimidinediamine drug to form a ratio, converts the drug into a prodrug. Progroups are typically linked to the functional group of the drug via bonds that can be split under specific conditions of use. In this way, a progroup is that portion of a proportion that unfolds to release the functional group under the specified conditions of use. As a specific example, an amide proportion of the formula -NH-C (0) CH3 comprises the progroup -C (0) CH3. "Fc receptor" refers to an element of the family of cell surface molecules that bind to the Fc portion (containing the specific constant region) of an immunoglobulin. Each Fc receptor is linked to immunoglobulins of a specific type. For example, the Fca receptor ("FcaR") binds to IgA, FceR binds to IgE, and Fc? R binds to IgG. The FcaR family includes the polymeric Ig receptor involved in IgA / IgM epithelial transport, the myeloid specific receptor RcaRI (also called CD89), the Fca / μR and at least two alternative IgA receptors (for a recent review, see Monteiro & amp; amp;; van de Winkel, 2003, Annu. Rev. Immunol, advanced e-publication. Fc RI is expressed in neutrophil cells, eosinophils, monocytes / macrophages, dendritic cells and kupfer cells. The FcaRI includes an alpha chain and the FcR gamma homodimer that carries an activation portion (ITAM) in the cytoplasmic domain and phosphorylates the Syk kinase. The FceR family includes two types, designated FceRI and FceRII (also known as CD23). FceRI is a high affinity receptor (it binds to IgE with an affinity of approximately 1010M_: L), found in mast cells, basophils, eosinophils that anchor monomeric IgE to the cell surface. FceRI possesses an alpha chain, a beta chain and the gamma chain homodimer discussed above. FceRII is a low affinity receptor expressed in mononuclear phagocytes, B lymphocytes, eosinophils and platelets. FceRII comprises a single polypeptide chain and does not include the gamma-chain homodimer. The Fc? R family includes three types, designated Fc? RI (also known as CD64), Fc? RII (also known as CD32) and Fc? RIII (also known as CD16). Fc? RI is a high affinity receptor (binds to IgGl with an affinity of 108M_1), found in mast, basophil, mononuclear, neutrophil, eosinophilic, dendritic and phagocytic cells that anchor monomeric IgG to the cell surface. The Fc? RI includes an alpha chain and the gamma chain dimer carried by FcaRI and FceRI. Fc? RII is a low affinity receptor expressed on neutrophils, monocytes, eosinophils, platelets and B lymphocytes. Fc? RII includes an alpha chain, and does not include the gamma-chain homodimer discussed above. Fc? RIII is a low affinity receptor (which binds to IgGl with an affinity of 5xl05M-1) expressed in NK cells, eosinophils, macrophages, neutrophils and mast. It comprises an alpha chain and the gamma homodimer carried by FcaRI, FceRI and Fc? RI. Experts in the art will recognize that the subunit structure and binding properties of these various Fc receptors, cell types that express them, are not fully characterized. The above discussion merely reflects the current state of the art with respect to these receptors (see for example, Immunobiology: The Immune System in Health &Disease, 5th Edition, Janeway et al., Eds, 2001, ISBN 0-8153-3642 -x, Figure 9.30 on pp. 371), and is not proposed to be limiting with respect to the innumerable receptor signaling cascades that can be regulated with the compounds described herein. "Degranulation mediated by the Fc receptor" or "Degranulation induced by the Fc receptor", refers to the degranulation that proceeds via a cascade of signal transduction of the Fc receptor initiated by the cross-linking of an Fc receptor. "IgE-induced degranulation" or "FceRI-mediated degranulation" refers to the degranulation that proceeds via the signal transduction cascade of the IgE receptor initiated by the cross-linking of FceRI linked to IgE. The crosslinking can be induced by a specific IgE allergen or other multivalent binding agent, such as an anti-IgE antibody. With reference to Figure 2, in mast cells and / 1 basophils, the FceRI signaling cascade leading to degranulation can be interrupted in two stages: upstream and downstream. The upstream stage includes all the processes that occur prior to the mobilization of calcium ions (illustrated as "Ca2 +" in Figure 2, see also Figure 3). The downstream stage includes mobilization of calcium ions and all processes downstream thereof. Compounds that inhibit FceRI-mediated degranulation can act at any point along the FceRI-mediated signal transduction cascade. Compounds that selectively inhibit FceRI-mediated degranulation upstream act to inhibit such portion of the FceRI signaling cascade upstream of the point at which calcium ion mobilization is induced. In cell-based assays, compounds that selectively inhibit upstream FceRI-mediated degranulation inhibit the degranulation of cells such as mast cells or basophils that are activated or stimulated with an IgE-specific allergen or binding agent (such as a anti-IgE antibody), but do not appreciably inhibit the degranulation of cells that are activated or stimulated with degranulation agents that derive the FceRI signaling pathway, such as, for example, the ionomycin of calcium ionophores and A23187. "IgG Induced Degranulation" or "Fc? RI Mediated Degranulation" refers to the degranulation that proceeds via the Fc? RI signal transduction cascade initiated by the cross-linking of Fc? RI bound to IgG. The crosslinking can be induced by a specific allergen of IgG or other multivalent binding agent, such as an anti-IgG or antibody fragment. Like the FceRI signaling cascade, in mast and basophil cells, the Fc? RI signaling cascade also leads to degranulation, which can be interrupted in the same two steps: upstream and downstream. Similar to FcRI-mediated degranulation, compounds that selectively inhibit upstream Fc? R-mediated degranulation act upstream of the point at which calcium ion mobilization is induced. In cell-based assays, compounds that selectively inhibit upstream FcγRI-mediated degranulation inhibit the degranulation of cells such as mast cells or basophils that are activated or stimulated with an IgG specific allergen or binding agent (such as as an anti-IgG antibody or fragment), but does not appreciably inhibit the degranulation of cells that are activated or stimulated with degranulation agent that derive the FcRI signaling pathway, such as, for example, the ionomycin of calcium ionophores and A23187 . "Ionophore-induced degranulation" or "Ionophore-mediated degranulation" refers to the degranulation of a cell, such as a mast or basophil cell, that occurs after exposure to a calcium ionophore, such as, for example, ionomycin or A23187. "Kinase Syk" refers to tyrosine kinase of the well-known 72 kDa non-receptor (cytoplasmic) spleen protein, expressed in B cells and other hematopoietic cells. Syk kinase includes two consensual domains Src-homology 2 (SH2) in series, which bind to tyrosine-based activation portions of the phosphorylated immunoreceptor ("ITAMS"), a "linker" domain and a catalytic domain (for a review of the structure and function of Syk kinase, see Sada et al., 2001, J. Biochem. (Tokyo) 130: 177-186); see also Turner et al. , 2000, Immunology Today 21: 148-154). Syk kinase has been extensively studied as an effector of B-cell receptor signaling (BCR) (Turner et al., 200, supra). Syk kinase is also critical for the tyrosine phosphorylation of multiple proteins which regulate important pathways leading from immunoreceptors, such as Ca2 + mobilization and mitogen-activated protein kinase (MAPK) cascades (see for example, Figure 2) and degranulation. Syk kinase also plays a critical role in the integrin signaling in neutrophils (see, for example, Mocsai et al., 2002, Immunity 16: 547-558). As used herein, Syk kinase includes kinases of any species of animals, including but not limited to homosapiens, apes, bovines, swine, rodents, etc., recognized as belonging to the Syk family. Specifically included are isoforms, splice variants, allelic variants, mutants, both naturally occurring and man-made. The amino acid sequences of such Syk kinases are well known and available from GENBANK. Specific examples of mRNA encoding different isoforms of human Syk kinase can be found in GENBANK access no. gi | 21361552 | ref | NM 003177.2 | , gi | 496899 | emb | Z29630.1 | HSSYKPTK [496899] and gi | 15030258 | gb | BC011399.1 | BC011399 [15030258], which are incorporated herein by reference. Experts in the art will appreciate that tyrosine kinases belonging to other families can have active sites or linkages that are similar in three-dimensional structure, with those of Syk. As a consequence of this structural similarity, such kinases referred to herein as "Syk mimics" are expected to catalyze the phosphorylation of substrates phosphorylated by Syk. Thus, it will be appreciated that such Syk mimic signal transduction cascades in which such Syk mimics play a role and biological responses effected by such Syk mimics and signaling cascades dependent on Syk mimics, can be regulated, and in particular inhibited, with the 2,4-pyrimidinediamine compounds described herein. "Syk-dependent signaling cascade" refers to a cascade of signal transduction in which the kinase plays a role. Non-limiting examples of such Syk-dependent signaling cascades include signaling cascades FcofRI, FceRI, FcyRI, Fc? RIII, BCR and integrin. "Autoimmune Disease" refers to those diseases which are commonly associated with non-anaphylactic hypersensitivity reactions (Type II, Type III and / or Type IV hypersensitivity reactions), which generally result as a consequence of the immune response mediated by the cells and / or humoral of the subject, to one or more immunogenic substances of endogenous and / or exogenous origin. Such autoimmune diseases are distinguished from diseases associated with anaphylactic hypersensitivity reactions (mediated by IgE or type I). 2, 4-pyrimidinediamine compounds The compounds of the invention are generally 2,4-pyrimidinediamine compounds according to structural formula (I): which include salts, hydrates, solvates and N-oxides thereof, wherein: L1 and L2 are each, independently from each other, selected from the group consisting of a direct link and a linker; R2 and R4 are as described in the following embodiments and examples; R5 is selected from the group consisting of R6 alkyl optionally substituted with one or more of the same or different R8 groups, (C1-C4) alkanyl optionally substituted with one or more of the same or different R8 groups, (C2-C4) alkenyl optionally substituted with one or more of the same or different R8 groups, and (C2-C4) alkynyl optionally substituted with one or more of the same or different R8 groups; each R6 is independently selected from the group consisting of hydrogen, an electronegative group, -0Rd, -SRd, haloalkyloxy (C1-C3), perhaloalkyloxy (C1-C3), -NRCRC, halogen, haloalkyl (C1-C3), perhaloalkyl ( C1-C3), -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, -N3, -S (0) Rd, -S (0) 2Rd, - S (0) 20Rd, -S (0) NRcRc, -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2R, -0S (0) 20Rd, -OS (0) NRcRc, -OS (0) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc, -C (NH) NRCRC, -OC (0) Rd, -SC (0) Rd, -OC ( 0) ORd, -SC (0) 0Rd, -0C (0) NRcRc, -SC (0) NRcRc, -OC (NH) NRCRC, -SC (NH) NRCRC, - [NHC (0)] nRd, - [ NHC (0)]? 0Rd, - [NHC (0)] pNRcRc and - [NHC (NH)] nNRcRc, aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, arylalkyl (C6-C16) optionally substituted with one or more of the same or different R8 groups, 5-10 element heteroaryl optionally substituted with one or more thereof or different s R8 groups, and 6-16 membered heteroarylalkyl optionally substituted with one or more of the same or different R8 groups; R8 is selected from the group consisting of Ra, Rb Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or R, -B (0Ra) 2, - B (NRCRC) 2, - (CH2) ffl-R, - (CHRa) ffl-Rb, -O- (CH2) ffl-Rb, -S- (CH2) ffl-R, -0-CHRaR, -0- CRa (Rb) 2, -O- (CHRa) m -Rb, -0- (CE2) Ir-CE (CR2) mRb] Rb, -S- CHR ^ -R15, -C (O) NH- ( CH2) ffl-Rb, -C (O) NH- (CHRa) m -Rb, -O- (CH2) ^ -C (O) NH- (CH2) m -Rb, -S-. { CH2) a, -C (0) NH- (CH2) a? -Rb, "O- (CHRa) mC (O) NH- (CHRa) m-Rb, -S- (CHRa) ffi-C (0) NH- (CHRa) E1-R, -NH- (CH2) m-Rb, -NH- (CHRa) m -Rb, -NH [(CH2)? Rb; |, -N [(CH2) mRb] 2, -NH-C (O) -NH- (CH2) m-Rb, -NH-C (0) - (CH2) ffl-CHRbRb and -NH- (CH2) mC (O) -NH- (CH2) m- Rb: each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-Cll), aryl (C5-C10), phenyl, arylalkyl (C6-) C16), benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, pipinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements, each Rb is a suitable group independently selected from the group consisting of = 0, -ORd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc, - S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -OS (0) 2ORd, -OS (0) 2NRcRc, -C (0) Rd, -C (0) ORd, -C (0) NRcRc, -C (NH) NRCRC, - C (NRa) NRCRC, -C (NOH) Ra, -C (NOH) NRCRC, -OC (0) R, -OC (0) ORd, -OC (0) NRcRc, -OC (NH) NRCRC, -OC (NRa) NRCRC, - [NHC (0)] nRd, - [NRaC (0)] pRd, - [NHC (O)] p0Rd, - [NRaC (O)] pORd, - [NHC (O)] pNRcRc, - [NRaC (O)] pNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa) J ^ NR ^ 0; each Rc is independently Ra, or, alternatively, each Rc is taken together with the nitrogen atom to which it is attached to form a heteroaryl or cycloheteroalkyl of 5 to 8 elements, which may optionally include one or more of the same or different heteroatoms additional and which is optionally substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3. In the compounds of structural formula (I), L1 and L2 independently represent a direct bond or a linker. Thus, as will be appreciated by those skilled in the art, the substituents R2 and / or R4 can be attached either directly to their respective nitrogen atoms or, alternatively, separated away from their respective nitrogen atoms by means of a linker. The identity of the linker is not critical and typical suitable linkers include, but are not limited to, (C 1 -C 6) alkyldi, (C 1 -C 6) alkanols, and (C 1 -C 6) heteroalkyldiyl, each of which may be optionally substituted with one or more of the same or different R8 groups, wherein R8 is as previously defined by the structural formula (I). In a specific embodiment, L1 and L2 are each, independently from each other, selected from the group consisting of a direct bond, (C1-C3) alkyldiyl optionally substituted with one or more of the same or different R8 groups, Rb or R9 groups suitable and heteroalkyldiyl of 1-3 elements, optionally substituted with one or more of the same or different suitable Ra, Rb or R9 groups, wherein R9 is selected from the group consisting of (C1-C3) alkyl, -ORa, -C (0) ORa, aryl (C5-C10) optionally substituted with one or more of the same or different halogens, phenyl optionally substituted with one or more of the same or different halogens, 5-10 element heteroaryl optionally substituted with one or more of the same or different halogens and 6-membered heteroaryl optionally substituted with one or more of the same or different halogens; and Ra and Rb are as previously defined by the structural formula (I). Specific R9 groups that can be used to replace L1 and L2 include, -0Ra, -C (0) ORa, phenyl, halophenyl and 4-halophenyl, wherein Ra is as previously defined by structural formula (I). In another specific embodiment, L1 and L2 are each, independently of each other, selected from the group consisting of methane, ethane and propane, each of which may optionally be monosubstituted with a group R9, wherein R9 is as previously defined. In all the above embodiments, the specific groups Ra which can be included in groups R9, are selected from the group consisting of hydrogen, alkyl (Cl-C6), phenyl and benzyl. In yet another specific embodiment, L1 and L2 are each a direct bond, such that the 2,4-pyrimidinediamine compounds of the invention are compounds according to the structural formula (Ia): which includes salts, hydrates, solvates and N-oxides thereof, wherein R2, R4, R5 and R6 are as previously defined by the structural formula (I). Additional specific moieties of the 2,4-pyrimidinediamine compounds of the invention are described below. In a first embodiment of the compounds of structural formula (I) and (la), L1, L2, R5, R6, R8, Ra, Rb, Rc, Rd, m and r are as previously defined, R 2 is where each R, 31, independently of each other, is methyl or (C 1 -C 6) alkyl and R is X is selected from the group consisting of N and CH, and selects from the group consisting of 0, S, SO, S02, SONR36, NH, NR35 and NR37, Z is selected from the group consisting of 0, S, SO, S02, SONR36, NH, NR35 and NR37. Each R35 is independently from each other, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the others two R35 are each, independently of each other, selected from the group consisting of hydrogen and R8. Each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl. Each R37 is independently selected from the group consisting of hydrogen and a progroup. R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl. In particular, Y is 0, Z is NH and X is N. R5 can be halogen and R6 is a hydrogen. In a second embodiment of the compounds of structural formula (I) and (la), L1, L2, R5, R6, R8, Ra, Rb, R °, Rd, m, n, R35, R36, R37, R38, X, Y and Z, are how they are defined previously, R is where each R ~ independently of each other, is methyl or (C1-C6) alkyl and R4 is In particular, Y is O, Z is NH and X is N, can be halogen and R is a hydrogen. In a particular aspect, Y is O, Z is NH, X is N and each R31 is methyl. In a third embodiment of the compounds of structural formula (I) and (Ia), L1, L2, R5, R6, R8, Ra, Rb, Rc, Rd, m, n, R31, R35, R36, R37, R38, X, Y and Z are as previously defined, R2 is and R4 is -R "'or XP Y and y is 1-6 In particular, Y is O, Z is NH and X is N. R5 can be halogen and R6 is hydrogen In a fourth embodiment of the compounds of formula structural (I) and (the), L1, L2, R5, R6, R8, Ra, R, Rc, Rd, m, n, R35, R36, R37, R38, X, Y and Z are as previously defined, R is The substitution about the phenyl ring R2 can be in positions 2, 3, 4, 5 or 6. In particular, Y is 0, Z is NH and X is N. R5 can be halogen and R6 is a hydrogen. In a fifth embodiment of the compounds of structural formula (I) and (la), L1, L2, R5, R6, R8, R, Rb, Rc, Rd, m, n, R35, R36, R37, R38, X, Y and Z are as previously defined, R2 is a phenyl group disubstituted with two groups Rb and R4 is The substitution about the phenyl ring R2 can be in positions 2,3, 2,4, 2, 5, 2,6, 3,4, 3,5, 3,6, 4,5, 4 , 6 or 5.6, with the proviso that the following compounds are not included: N4- (2,2-Dimethyl-3-oxo-4H-5 ~ pyrid [1,4] oxazin-6-yl) ~ N2 - (3-chloro-4-methoxyphenyl) -5-fluoro-2,4-pyrimidinediamine; N 4 - (2, 2-Dimethyl-3-oxo-4 H -5-pyrid [1,4] oxazin-6-yl) - N 2 - (3,5-dimethoxyphenyl) -5-fluoro-2,4-pyrimidinediamine; N2- (3,4-Dichlorophenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2,4-pyrimidinediamine; N4- (2, 2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -N2- (3-fluoro-4-methoxyphenyl) -5-fluoro-2, 4- pyrimidindiamine; N2- (3, 5-Dichlorophenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2,4-pyrimidinediamine; and N2- (3-Chloro-4-trifluoromethoxy-phenyl) -N4- (2, 2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2, 4 -pyrimidindiamine.

In particular, Y is O, Z is NH and X is N. R5 can be halogen and R6 is a hydrogen. In certain aspects, each Rb independently is selected from (C1-C6) alkoxy, (C1-C16) alkyl, perhaloalkyls (C1-C6), halogens, carboxylic acid, carboxylic ester, carboxamides, sulfonamides and imidazoles. In a sixth embodiment of the compounds of structural formula (I) and (la), L1, L2, R5, R6, R8, Ra, Rb, Rc, Rd, m, n, R35, R3d, R37, R38, X, Y and Z are as previously defined, R2 is a trisubstituted phenyl group with three R groups and R4 is The substitution about the phenyl ring R2 can be in the positions 2,3,4, 2,3,5, 2,3,6, 2,4,5, 2,4,6, 2,5,6, 3, 4.5, 3.4.6, 3.5.6, or 4.5.6, with the proviso that the following compounds are not included. N2- (3-Chloro-4-methoxy-5-methylphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro- 2,4-pyrimidinediamine; N2- (3-Chloro-4-hydroxy-5-methylphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro- 2,4-pyrimidinediamine; and N2- (3, 5-Dimethyl-4-methoxyphenyl) -N4- (2, 2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2 , 4-pyrimidindiamine. In particular, Y is O, Z is NH and X is N. R5 can be halogen and R6 is a hydrogen. In certain aspects, each Rb is independently selected from (C1-C6) alkoxy, (C1-C16) alkyl, perhaloalkyls (C1-C6), halogens, carboxylic acid, carboxylic esters, carboxamides, sulfonamides. In certain embodiments, the compounds described in U.S. Patent Application Serial No. 10 / 631,029, filed July 29, 2003 and 10 / 355,543, filed January 31, 2003, respectively, are not included within the scope of the invention. present request. In a seventh embodiment of the compounds of structural formula (I) and (Ia), R5, R6, L1 and L2 are as previously defined, R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 and heteroaryl groups of 5-15 elements, optionally substituted with one or more of the same or different R8 groups, R4 is R a is aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, or optionally substituted phenyl with one or more of the same or different groups R8 and R8 is as previously defined. In an eighth embodiment of the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2 are as previously defined, R2 is selected from the group consisting of wherein each R21 is independently a halogen atom or an alkyl optionally substituted with one or more of the same or different halo groups, R22 and R23 are each, independently of each other, a hydrogen atom, a methyl or ethyl group, optionally substituted with one or more of the same or different halo groups and R4 is a (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups. In a ninth embodiment of the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2 are as previously defined, R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3- 8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups and heteroaryl of 5-15 elements optionally substituted with one or more of the same or different groups R, R is R 35 is a hydrogen or R 8; and R 45 is a (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups. In a tenth embodiment, the compounds of structural formula R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and optionally substituted 5-15 element heteroaryl with one or more of the same or different R8 groups, R4 is selected from the group consisting of hydrogen, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, optionally substituted (C3-C8) cycloalkyl with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and heteroaryl of 15 elements optionally substituted with one or more of the same or different R8 groups, and R55 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, cycloalkyl (C3-C8) optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and heteroaryl of 5-15 elements optionally substituted with one or more of the same or different R8 groups. In a tenth embodiment of the compounds of structural formulas (I) and (the), R5, R6, R8, L1 and L2 are as are previously defined, R1 is and R4 is selected from the group consisting of hydrogen, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8, cyclohexyl groups optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements, optionally substituted with one or more of the same or different R8 groups, aryl (C5-) C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl optionally substituted with one or more of the same or different groups R8 In a tenth second embodiment of the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2 are as are previously defined, R2 is R4 is selected from the group consisting of hydrogen, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different groups R8, cyclohexyl optionally substituted with one or more of the same or different groups R8, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different groups R8, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R groups, and heteroaryl of 5-15 elements optionally substituted with one or more of the same or different R8 groups, and each R35 individually is a hydrogen or a suitable R8.

In a thirteenth embodiment of the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2 are as previously defined, R2 is selected from the group consisting of optionally substituted (C1-C6) alkyl with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3 -8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different groups R8, and 5-15 element heteroaryl optionally substituted with one or more of the same or different groups R8, R4 is and R35 is a suitable hydrogen or R8. In a fourteenth embodiment, the compounds of structural formulas (I) and (la), R5 and R6, R8, L1 and L2 are as previously defined, R4 is a substituted phenyl group, substituted with the same or different group R8 and R2 is 1 to 6. In one aspect, the phenyl group R 4 is di or tri-substituted with the same or different R 8 groups, and in particular, halogen atoms. In particular, R 4 can be substituted at positions 3 and 4 relative to the bond at the N 4 amine, particularly with halogen atoms and / or alkoxy groups. In a fifteenth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is a substituted phenyl group, substituted with the same or different R8 groups and R2 is In one aspect, the phenyl group R4 is di or tri-substituted with the same or different R8 groups, and in particular, halogen atoms. In particular, R 4 can be substituted at positions 3 and 4 relative to the bond at the N 4 amine, particularly with halogen atoms and / or alkoxy groups. In a sixteenth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is a substituted phenyl group, substituted with the same or different R8 groups and R2 is' • In one aspect, the phenyl group R4 is di or tri-substituted with the same or different R8 group, and in particular, halogen atoms. In particular, R 4 can be substituted at positions 3 and 4 relative to the bond at the N 4 amine, particularly with halogen atoms and / or alkoxy groups. In a seventeenth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is a phenyl group, substituted with the same or different R8 groups and R2 is wherein R35 is an alkylalkoxy group, and particular is In one aspect, the phenyl group R4 is di or tri-substituted with the same or different group R8, and in particular, halogen atoms. In particular, R 4 can be substituted at positions 3 and 4 relative to the bond at the N 4 amine, particularly with halogen atoms and / or alkoxy groups. In a tenth eighth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is a substituted phenyl group, substituted with the same or different R8 group , and R2 is where R35 is an alkyl group, and in particular is In one aspect, the phenyl group R 4 is di or tri-substituted with the same or different R 8 groups, and in particular, halogen atoms. In particular, R 4 can be substituted at positions 3 and 4 relative to the bond at the N 4 amine, particularly with the halogen atoms and / or alkyl groups. In a tenth ninth embodiment, the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2, are as defined previously, R4 is and R2 is and in particular, it is substituted in position 3 or 4, with isoxazole. And it is selected from the group consisting of O, S, SO, S02, SONR36, NH and NR37. Z is selected from the group consisting of 0, S, SO, S02, SONR36, NH and NR37. Each R35 is independently from each other, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 each, if present, independently of each other, are selected from the group consisting of hydrogen and R8. Each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl. Each R37 is independently selected from the group consisting of hydrogen and a progroup. R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl. In certain aspects, R37 is selected from the group consisting of aryl, arylalkyl, heteroaryl, Ra, Rb-CRaRb-0-C (0) R8, -CRaRb-0-PO (OR8) 2, -CH2-0-PO ( OR8) 2, -CH2-PO (OR8) 2, -C (0) -CRaRb-N (CH3) 2, -CRaRb-0-C (0) -CRaRb-N (CH3) 2, -C (0) R8, -C (0) CF3 and -C (0) -NR8-C (0) R8. In one aspect, Y is oxygen, Z is NH and one or more of R35 is an alkyl group, and in particular, a methyl group. Surely, two R35 form a dialkyl gem moiety, in particular, a gem dimethyl moiety adjacent to the NH In a twentieth embodiment, the compounds of the structural formulas (I) and (la), R5, R6, R8, L1 and L2, are as defined previously, R4 is j wherein each R35 is as defined above, and in particular both are halogen atoms, for example, fluorine, and R2 is a substituted phenyl group, substituted with the same or different R8 groups. In one aspect, the phenyl group R2 is di or tri-substituted with the same or different R8 groups and in particular, halogen atoms. In particular, R 2 can be substituted at positions 3 and 5 relative to the binding to the N 2 amine, particularly with halogen atoms and / or alkoxy groups. In a twenty-first embodiment, the compounds of formulas (I) and (la), R5, R5, R8, L1 and L2, are as previously defined, R is > where Y and Z are as defined above, and Rj2 is and in particular, is substituted at position 3 6 4 with isoxazole. In an aspect of the thirty-ninth modality with with respect to R4, Y is NH and Z is 0, for example, In a twenty-second embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as defined previously, R4 is, wherein R8 and Rc are as defined above and R2 is a phenyl group substituted on the position 3 or 4 with In one aspect, -OR8, R8 is a hydrogen atom. In a twenty-third embodiment, the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2, are as defined previously, R4 is and R2 is a substituted phenyl group, substituted with at least two of the same or different R8 groups as defined above. Suitable examples include compounds 340, 343, 349, 350 and 351. In a twenty-fourth embodiment, the compounds of structural formulas (I) and (la), R5, R6, R8, L1 and L2, are as previously defined, R4 is In a twenty-fifth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is - where Y and R35 are as defined above. Suitable examples include compounds 368, 381, 382, 383, and 384. In a twenty-sixth embodiment, the compounds of structural formulas (I) and (la), R5, R5, R8, L1 and L2, are as previously defined, R4 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more thereof or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl optionally substituted with one or more of the same or different groups R8, and R2 is, wherein R35 is as defined above. Suitable examples include compounds 205 and 206. In a twenty-seventh embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is a phenyl group substituted with one or more of the same R8 groups. Suitable examples include compounds 328, 329, 330, 341, 553, 554, 555, 556, 559, and 560.

In a twenty-eighth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements, optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more thereof or different R8 groups, and 5-15 element heteroaryl, optionally substituted with one or more of the same or different R8 groups, and R2 is 'where Y is as defined above or is NR35 and R35 is as defined above. Suitable examples include compounds 1070, 1071, 1073, 1074, 1075, 1076, 1078, 1080, 1085, 1091 and 1092. In a twenty-ninth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is where R1 is a substituted phenyl group or an indazole, substituted with one or more of the same or different R8 groups as defined above. Suitable examples include compounds 1251, 1252, 1253, 1254 and 1255. In a thirtieth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R4 is where each R independently is as it is described above and R? 2 e. s _, Suitable examples include compounds 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234 , 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 1281, 1283, 1283, 1284, 1285, 1287, 1288, 1289, 1290 and 1291. In a thirteenth embodiment , the compounds of formulas (I) and (la), R5, R6, R8, L1 and L2, are as defined previously, R4 is where Rz is a hydrogen or lower alkyl group, Rx and Ry are each independently, lower alkyl groups, or taken together form a cycloalkyl and Rp is a halogen atom or a lower alkyl group and R2 is as is defined above. Suitable examples include compounds 402, 403, 407, 408, 409 and 410. In a twentieth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined , R2 is one, independently from each other, selected from the group consisting of alkyl, alkoxy, halogen, haloalkoxy, aminoalkyl and hydroxyalkyl; In a twenty-third embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined, R2 is selected from alkyl (Cl-C6), optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl, optionally substituted with one or more of the same R, R, R, Ra, R, Rc, Rd, m and n are as described above; each R21, R22 and R23 are each independently of each other, as described above and in particular, an R28 alkylered group individually is a halogen or alkoxy; R29 is a (C1-C6) alkyl or (C3-C9) cycloalkyl; R30 is an alkyl group or a halogen; X is selected from the group consisting of N and CH; Y, Z, R35, R36, R37 and R38 are as described above; each R46, R47 and R48 independently are selected from the group consisting of a hydrogen, alkyl, alkoxy, hydroxyl, halogen, isoxazole, piperazino, N-alkylpiperazino, morpholino and CH3NHC (O) CH20-, with the proviso that R46, R47 and R48 are not all hydrogen and when one of R46, R47 or R48 is isoxazole, piperazino, N-alkylpiperazino, morpholino or CH3NHC (O) CH20, then the remaining R46, R47 or R48 are hydrogen; R50 is an alkyl group or - (CH2) qOH; q is an integer from 1 to 6; R52 is an alkyl group or a substituted alkyl group p is 1, 2 or 3; and K = 1-8. In a thirty-fourth embodiment of the compounds of structural formulas (I) and (a) R2, R4, R5, L1 and L2 are as previously described by their respective structures (I) and (a), with the proviso that R2 is not 3,4,5-tri-ethoxyphenyl, 3,4,5-trialkoxyphenyl (C1-C6) or wherein R21, R22 and R23 are as defined by R1, R2 and R3, respectively, of U.S. Patent Application No. 6,235,746, a description of which is incorporated by reference. In a specific embodiment of this first embodiment, R21 is hydrogen, halo, straight or branched chain alkyl (Cl-C6), optionally substituted with one or more of the same or different groups R25, hydroxyl, (C1-C6) alkoxy optionally substituted with one or more of the same or different R25 groups, thiol (-SH), alkylthio (C1-C6) optionally substituted with one or more of the same or different phenyl or R25 groups, amino (-NH2), -NHR26 or -NR26R26; R22 and R23 are each, independently of each other, a straight or branched chain alkyl of (C1-C6), optionally substituted with one or more of the same or different R25 groups; R 25 is selected from the group consisting of halo, hydroxyl, (C 1 -C 6) alkoxy, thiol, (C 1 -C 6) alkylthio, (C 1 -C 6) alkylamino, and (C 1 -C 6) dialkylamino; and each R26 is independently (C1-C6) alkyl optionally substituted with one or more of the same or different R25 groups, or a -C (0) R27, wherein R27 is a (C1-C6) alkyl, optionally substituted with one or more of the same or different R25 groups. In another specific embodiment, R21 is methoxy optionally substituted with one or more of the same or different halo groups and / or R22 and R23 are each independently of each other, a methyl or ethyl optionally substituted with one or more of the same or different groups halo. In a thirty-fifth embodiment, the compounds of structural formulas (I) and (Ia), R5, R6, R8, L1 and L2, are as previously defined; R2 is R5, R6, R30, R35 and x are as defined above. In certain modalities, x is 2 to 4. In other embodiments, R 35 is a methyl group. In still further embodiments, R 30 is chloro, methyl or trifluoromethyl. In still other embodiments, R5 is fluorine and Rd is hydrogen. In a twenty-sixth embodiment, the 2,4-pyrimidinediamine includes those compounds in accordance with structures I and I (a), wherein R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, optionally substituted 3-8-element cycloheteroalkyl. with one or more of the same or different R8 groups, aryl (C1-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and heteroaryl of 5-15 elements optionally substituted with one or more of the same or different R8 groups. R4 is R5 f Re and Re are as described above. In certain embodiments, R5 is a fluorine atom and R6 is a hydrogen atom. In certain embodiments, R 2 is a di or tri-substituted phenyl group. In a thirty-seventh embodiment, the invention pertains to 2,4-pyrimidinediamine compounds in accordance with structures I and I (a) wherein R2 is and R5, R6, R22 and R23, R46, R47 and R48 are as defined above, each R21, independently of each other, is an alkyl group. In certain embodiments, R5 is a fluorine atom and R6 is a hydrogen atom. In a thirty-eighth embodiment, the present invention relates to 2,4-pyrimidinediamine compounds according to structures I and I (a), wherein R2 is R5, R6, R8, R21, R23, R28, R35, R36, R37, R38, Y, Z, Ra, Rb, Rc, Rd, myn are as described above, and X is selected from the group consisting of N and CH. In a particular embodiment, R28 is methoxy. In another embodiment, R23 is methyl. In particular embodiments, R21 is a methyl group. In other modalities, each R28 is chlorine. In still further embodiments, R21 is a methyl group and at least one R28 is a chlorine. In another embodiment, R28 is a methoxy. In a thirty-ninth embodiment, the present invention provides pyrimidinediamine compounds in accordance with structures I and I (a), wherein R2 is each R28, R29, Ra, Rb, Rc, Rd, m and n, X, Y, Z, each R35, each R36, each R37 and R38 are as described above. In certain embodiments, R29 is a t-butyl group. In other embodiments, R21 is a methyl group. In certain modalities, each R28 is a chlorine. In yet another embodiment, R21 is a methyl group and at least one of R28 is a chlorine. In a fortieth embodiment, the invention pertains to 2-pyrimidinediamine compounds according to structures I and I (a) wherein R2 is R, 21 ±, each R, 28o, Ra, R ", Rc, Ra, m, n, p, X, Y, Z, each RJS, each R36, each R37 and R38 are as described above. R21 is a methyl group In other embodiments, each R28 is a chlorine In still other embodiments, R21 is a methyl group and at least one of R28 is a chlorine In yet another aspect, p is 1 or 2. In one embodiment, Forty-first embodiment, the invention relates to 2,4-pyrimidinediamine compounds in accordance with structures I and I (a) wherein R2 is R5, R6, R8, R21, each R28, Ra, Rb, Rc, Rd, m, n, q, X, Y, Z, R35, R36, R37, R38, R50, and R52 are as described above. In certain aspects, R50 is -CH2CH2-0H or methyl. In another aspect, R52 is trifluoromethyl. In yet another aspect, at least one of R28 is a chlorine. In yet another aspect, R50 is a methyl and at least one R28 is a chlorine. In a forty-second embodiment, applicable to the first through the forty-first embodiment, R5 of the pyrimidine ring is a halogen atom, such as fluorine, and R6 of the pyrimidine ring is a hydrogen atom. In a forty-third modality, L1 and L2 are covalent bonds for the modalities identified above. Also, combinations of the above, first to forty-third modalities are specifically described.

Those skilled in the art will appreciate that the 2,4-pyrimidinediamine compounds described herein may include functional groups that can be masked with progroups to create prodrugs. Such prodrugs are usually, but need not be, pharmacologically inactive until they become their active prodrug form. However, many of the active 2,4-pyrimidinediamine compounds described in TABLE 1, include proportions that can be hydrolyzed or otherwise split under conditions of use. For example, ester groups are commonly subjected to acid-catalyzed hydrolysis to provide the original carboxylic acid when exposed to acidic conditions of the stomach, or base-catalyzed hydrolysis when exposed to the basic conditions of the intestine or blood. In this way, when administered to a subject orally, 2,4-pyrimidinediamines including ester portions can be considered prodrugs of their corresponding carboxylic acid, with respect to whether the ester form is pharmacologically active. With reference to TABLE 1, numerous esters containing 2,4-pyrimidinediamines of the invention are active in their "prodrug", ester form. In the prodrugs of the invention, any available functional portion can be masked with a progroup to provide a prodrug. Functional groups within the 2,4-pyrimidinediamine compounds that can be masked with progroups for inclusion in a proportion include, but are not limited to, amines (primary and secondary), hydroxyls, sulfanyls (thiols), carboxyls, etc. Innumerable progroups suitable for masking such functional groups to give proportions that can be split under the desired conditions of use, are known in the art. All these progroups, alone or in combinations, can be included in the prodrugs of the invention. In an illustrative embodiment, the prodrugs of the invention are compounds according to structural formula (I) in which, Rc and Rd can be, in addition to their previously defined alternatives, a progroup. Those skilled in the art will appreciate that many of the compounds and prodrugs of the invention, as well as the various composite species specifically described and / or illustrated herein, may exhibit the phenomenon of tautomerism, conformational isomerism, geometric isomerism and / or isomerism. optical. For example, the compounds and prodrugs of the invention may include one or more chiral centers and / or double bonds and as a consequence, may exist as stereoisomers, such as double bond isomers (ie, geometric isomers), enantiomers and diastereomers and mixtures thereof, such as racemic mixtures. As another example, the compounds and prodrugs of the invention may exist in various tautomeric forms, including the enol form, the keto form and mixtures thereof. As the various names of compounds, formulas and schemes of compounds within the specification and claims may represent only one of the possible tautomeric, isomeric, conformational isomeric, optical or geometric isomeric forms, it is to be understood that the invention encompasses any of the tautomeric forms, Isomeric conformational, optical isomeric and / or geometric isomeric of the compounds or prodrugs having one or more of the utilities described herein, as well as mixtures of these various different isomeric forms. In cases of limited rotation about the core structure of 2,4-pyrimidinediamine, atropisomers are also possible and are also specifically included in the compounds of the invention. However, experts in the art will appreciate that when the lists of alternative substituents include elements which, due to valence requirements or other reasons, can not be used to substitute a particular group, the list is proposed to be read in the context to include those elements of the list that are suitable to replace the particular group. For example, those skilled in the art will appreciate that while all alternatives listed for R can be used to replace an alkyl group, certain alternatives, such as = 0, can not be used to replace a phenyl group. It is understood that only possible combinations of pairs of substituent groups are proposed. The compounds and / or prodrugs of the invention can be identified by either their chemical structure or their chemical name. When the chemical structure and the chemical name come into conflict, the chemical structure is determinative of the identity of the specific compound. Depending on the nature of the various substituents, the 2,4-pyrimidinediamine compounds and prodrugs of the invention may be in the form of salts. Such salts include salts suitable for pharmaceutical uses ("pharmaceutically acceptable salts"), salts suitable for veterinary use, etc. Such salts may be derived from acids or bases, as is well known in the art In one embodiment, the salt is a salt In general, pharmaceutically acceptable salts are those salts that retain substantially one or more of the desired pharmacological activities of the parent compound and which are suitable for administration to humans.Pharmaceutically acceptable salts include acid addition salts formed with acids inorganic or organic acids Suitable inorganic acids for forming pharmaceutically acceptable acid addition salts include, but are not limited to, hydrohalide acids (eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), sulfuric acid, nitric acid , phosphoric acid and the like. Suitable agents for forming pharmaceutically acceptable acid addition salts include, by way of example and without limitation, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanpropionic acid, glycolic acid, oxalic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, palmitic acid, benzoic acid, 3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, alkylsulfonic acids (eg, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, etc.), arylsulfonic acids (for example, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, cycloalkylsulfonic acids (for example, camphorsulfonic acid), 4-methylbicyclo [2.2.2] -oct-2-en-l-carboxylic acid, acid g lucoheptonic, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthonic acid, salicylic acid, stearic acid, muconic acid and the like. The pharmaceutically acceptable salts also include salts formed when an acidic proton present in the parent compound is either replaced by a metal ion (eg, an alkali metal ion, an alkaline earth metal ion or an aluminum ion), an ion of ammonium or coordinated with an organic base (for example, ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, morpholine, piperidine, dimethylamine, diethylamine, etc.). The 2,4-pyrimidinediamine compounds of the invention, as well as the salts thereof, can also be in the form of hydrates, solvates and N-oxides, as are well known in the art.

Synthesis Methods The compounds and prodrugs of the invention can be synthesized via a variety of original synthetic routes using commercially available starting materials and / or starting materials prepared by conventional synthetic methods. Suitable exemplary methods that can be routinely adapted to synthesize the 2,4-pyrimidinediamine compounds and prodrugs of the invention are found in U.S. Patent No. 5,958,935, U.S. Patent Application 10 / 355,543, filed January 31, 2003 (Application US200410029902-A1), WO 03/063794, published February 19, 2004, descriptions of which are incorporated herein by reference. All compounds of structural formulas (I), (la) and (II) can be prepared by routine adaptation of these methods. A variety of exemplary synthetic routes that can be used to synthesize the 2,4-pyrimidinediamine compounds of the invention are described in Reaction Schemes (I) - (XI) below. In Reaction Schemes (I) - (XI), similar numbered compounds have similar structures. These methods can be routinely adapted to synthesize the prodrugs in accordance with structural formula (II). In an exemplary embodiment, the compounds can be synthesized from substituted or unsubstituted uracils or thiouracils as illustrated in Reaction Scheme (I), below: Reaction Scheme (I) the halide CA is more reactive towards the 12 nucleophiles 10 excess 14 In the Reaction Scheme (I), R2, R4, R5, R6, L1 and L2 are as previously defined by the structural formula (I); X is a halogen (e.g., F, Cl, Br or I) and Y and Y 'are each, independently of each other, selected from the group consisting of O and S. With reference to Reaction Scheme (I), uracil or thiouracil 2 is dihalogenated in positions 2- and 4- using standard halogenating agent POX3 (or other standard halogenating agent), under standard conditions to give 2,4-bishalopyrimidine 4. Depending on the of the R5 substituent, in pyrimidine 4, the halide at the C4 position is more reactive towards the nucleophiles than the halide at the C2 position. This differential reactivity can be exploited to synthesize 2,4-pyrimidinediamines according to structural formula (I), first reacting 2,4-bishalopyrimidine 4 with an equivalent of amine 10, providing 2-halo-4-pyrimidinamine 4N-substituted 8, followed by amine 6 to give a 2,4-pyrimidinediamine in accordance with structural formula (I). 2N, 4N-bis (substituted) -2,4-pyrimidinediamines 12 and 14 can be obtained by reacting 2,4-bishalopyrimidine 4 with 6 or 10 excess, respectively. In many situations, the C4 halide is more reactive towards nucleophiles, as illustrated in the Reaction Scheme. However, as will be recognized by those skilled in the art, the identity of the R5 substituent may alter this reactivity. For example, when R5 is trifluoromethyl, a 50:50 mixture of 4N-substituted 4-pyrimidinamine 8 and the corresponding 2N-substituted 2-pyrimidinamine is obtained. With respect to the identity of the R5 substituent, the regioselectivity of the reaction can be controlled by adjusting the solvent and other synthetic conditions (such as temperature), as is well known in the art. The reactions represented in the Reaction Scheme (I) can proceed more quickly when the reaction mixtures are heated via microwaves. When heated in this manner, the following conditions can be used: heat at 175 ° C in ethanol for 5-20 minutes in a Smith Reactor (Personal Chemistry) in a sealed tube (at 20 bars of pressure). The initiator materials uracil or thiouracil 2 can be purchased from commercial sources, or prepared using standard techniques of organic chemistry. Commercially available uracils and thiouracils that can be used as starting materials in Reaction Scheme (I) include, by way of example and without limitation, uracil (Aldrich # 13,078-8; CAS Registry 66-22-8); 2-thio-uracil (Aldrich # 11,558-4; CAS Registry 141-90-2); 2,4-dithiouracil (Aldrich # 15,846-1; CAS Registry 2001-93-6); 5-acetouracil (Chem. Sources Int'l 2000; CAS Registry 6214-65-9); 5-azidouracil; 5-aminouracil (Aldrich # 85,528-6; CAS Registry 932-52-5); 5-bromouracil (Aldrich # 85.247-3; CAS Registry 51-20-7); 5- (trans-2-bromovinyl) -uracil (Aldrich # 45,744-2; CAS Registry 69304-49-0); 5- (trans-2-chlorovinyl) -uracil (CAS Registry 81751-48-2); Uracil-5-carboxylic acid (2,4-dihydroxypyrimidine-5-carboxylic acid hydrate; Aldrich # 27,770-3; CAS Registry 23945-44-0); 5-chlorouracil (Aldrich # 22,458-8; CAS Registry 1820-81-1); 5-cyanouracil (Chem. Sources Int'l 2000; CAS Registry 4425-56-3); 5-ethyluracil (Aldrich # 23,044-8; CAS Registry 4212-49-1); 5-eteniluracil (CAS Registry 37107-81-6); 5-fluorouracil (Aldrich # 85,847-1; CAS Registry 51-21-8); 5-iodouracil (Aldrich # 85,785-8; CAS Registry 696-07-1); 5-methyluracil (tintine; Aldrich # 13,199-7; CAS Registry 65-71-4); 5-nitrouracil (Aldrich # 85.276-7; CAS Registry 611-08-5); uracil-5-sulfamic acid (Chem. Sources Int'l 2000; CAS Registry 5435-16-5); 5- (trifluoromethyl) -uracil (Aldrich # 22,327-1; CAS Registry 54-20-6); 5- (2, 2, 2-trifluoroethyl) -uracil (CAS Registry 155143-31-6); 5- (pentafluoroethyl) -uracil (CAS Registry 60007-38-3); 6-aminouracil (Aldrich # A5060-6; CAS Registry 873-83-6) uracil-6-carboxylic acid (orotic acid; Aldrich # 0-840-2; CAS Registry 50887-69-9); 6-methyluracil (Aldrich # D11, 520-7; CAS Registry 626-48-2); Uracil-5-amino-6-carboxylic acid (5-aminoorotic acid; Aldrich # 19,121-3; CAS Registry # 7164-43-4); 6-amino-5-nitrosouracil (6-amino-2,4-dihydroxy-5-nitrosopyrimidine; Aldrich # 27,689-8; CAS Registry 5442-24-0); uracil-5-fluoro-6-carboxylic acid (5-fluoroorotic acid; Aldrich # 42,513-3; CAS Registry 00000-00-0); and uracil-5-nitro-6-carboxylic acid (5-nitroorotic acid; Aldrich # 18,528-0; CAS Registry 600779-49-9). The additional 5-, 6-, and 5,6-substituted uracils and / or thiouracils are available from General Intermediates of Canada, Inc., Edmonton, Alberta, CA (ww., Generalintermediates. Com) and / or Interchim, France ( www.interchim.com), or they can be prepared using standard techniques. Countless references of texts that show suitable synthetic methods are provided below. Amines 6 and 10 can be purchased from commercial sources, or alternatively, can be synthesized using standard techniques. For example, suitable amines can be synthesized from nitro precursors using standard chemistry. Specific exemplary reactions are provided in the Examples section. See also, Vogel 1989, Practical Organic Chemistry, Addison Wesley Longman, Ltd. and John Wiley & Sons, Inc. Experts in the art will recognize that in some cases, amines 6 and 10 and / or substituents R5 and / or R6 in uracil or thiouracil 2 may include functional groups that require protection during synthesis. The exact identity of any of the protective group (s) used will depend on the identity of the functional group being protected, and will be apparent to those of skill in the art. The guide for selecting appropriate protective groups, as well as synthetic strategies for their attachment and removal, can be found, for example, in Greene & Wuts, Protective Groups in Organic Synthesis, 3d Edition, John Wiley & Sons, Inc., New York (1999) and references cited in this document (subsequently "Greene &Wuts"). A specific embodiment of Reaction Scheme (I) using 5-fluorouracil (Aldrich # 32.937-1), as a starting material, is illustrated in the Reaction Scheme (la), below: Reaction Scheme (la) 1 equlv In the Reaction Scheme (la), R2, R4, L1 and L2 are as previously defined by the Reaction Scheme (I). In accordance with Reaction Scheme (la), 5-fluorouracil 3 is halogenated with P0C13 to provide 2,4-dichloro-5-fluoropyrimidine 5, which is then reacted with excess of amine 6 or 10, to give 5- fluoro-2, 4-pyrimidinediamine N2, 4-bis-substituted 11 13, respectively. Alternatively, 2N, 4N-disubstituted 5-fluoro-2, 4-pyrimidinediamine, bis 9, can be obtained by reacting 2,4-dichloro-5-fluoropyrimidine 5, with one equivalent of amine 10 (to give 5-fluoro-4). 2-chloro-N4-substituted pyrimidinamine 7), followed by one or more equivalents of amine 6. In another exemplary embodiment, the 2,4-pyrimidinediamine compounds of the invention can be synthesized from substituted or unsubstituted cytokines as is illustrated in the Reaction Schemes (lia) and (Ilb), below: Reaction Scheme (lia) Reaction Scheme (Ilb) 27 29 (1) In the Reaction Schemes (lia) and (Ilb), R2, R4, R5, R6, L1, L2 and X, are as previously defined by the Reaction Scheme (I) and PG represents a group protective. With reference to the Reaction Scheme (Ha), the cytokine 20 exocyclic amine 20, is first protected with a suitable protective group PG to give N4-protected cytokine 22. For specific guidance pertaining to protective groups useful in this context, see , Vorbrüggen and Ruh-Pohlenz, 2001, Handbook of Nucleoside Synthesis, John Wiley & Sons, NY, pp. 1-631 ("Vorbrüggen"). The protected cytokine 22 is halogenated at the C2 position using a standard halogenation reagent under standard conditions to give 2-chloro-4N-protected-4-pyrimidinamine 24. The reaction with amine 6 followed by deprotection of the exocyclic amine C4 and the reaction with amine 10, provides a 2,4-pyrimidinediamine in accordance with structural formula (I). Alternatively, with reference to the Reaction Scheme (Hb), the cytokine 20 can be reacted with the amine 10 or protected amine 21, to give N4-substituted cytokine 23 or 27, respectively. These substituted cytokines can then be halogenated as previously described, deprotected (in the case of N4-substituted cytokine 27), and reacted with amine 6 to give 2,4-pyrimidinediamine in accordance with structural formula (I). Commercially available cytokines that can be used as starting materials in the Reaction Schemes (Ha) and (Hb) include, but are not limited to, cytokine (Aldrich # 14, 201-8; CAS Registry 71-30-7); N4-acetylcytokine (Aldrich # 37,791-0; CAS Registry 14631-20-0); 5-Fluorocytokine (Aldrich # 27,159-4; CAS Registry 2022-85-7); and 5- (trifluoromethyl) -cycline. Other suitable cytokines useful as starting materials in the Reaction Schemes (Ha) are available from General Intermediates of Canada, Inc., Edmonton, Alberta, CA (www. Generalintermediates.co) and / or Interchim, France (www. interchim.com), or they can be prepared using standard techniques. Countless references of texts that show suitable synthetic methods are provided below.

In yet another exemplary embodiment, the 2,4-pyrimidinediamine compounds of the invention can be synthesized from substituted or unsubstituted 2-amino-4-pyrimidinoles as illustrated in Reaction Scheme (III), below: Reaction Scheme (III) (0 34 In the Reaction Scheme (III), R2, R4, R5, R6, L1, L2 and X are as previously defined for the Reaction Scheme (I) and Z is a leaving group as discussed in more detail in conjunction with Reaction Scheme IV, infra. With reference to Reaction Scheme (III), 2-amino-4-pyrimidinol 30, it is reacted with amine 6 (or optionally protected amine 21) to give, 4-pyrimidinol N2-substituted 32, which is then halogenated as it is previously described to give N2-substituted 4-halo-2-pyrimidinamine 34. Optional deprotection (e.g., if the protected amine 21 is used in the first stage), followed by the reaction with the amine 10, it provides a 2,4-pyrimidinediamine according to the structural formula (I). Alternatively, the pyrimidinol 30 can be reacted with the acylating agent 31. The commercially available 2-amino-4-pyrimidinoles that can be used as starting materials in the Reaction Scheme (III) include, but are not limited to, , 2-amino-6-chloro-4-pyrimidinol hydrate (Aldrich # A4702-8; CAS Registry 00000-00-0) and 2-amino-6-hydroxy-4-pyrimidinol (Aldrich # A5040-1; CAS Registry 56-09-7). Other 2-amino-4-pyrimidinoles useful as starting materials in the Reaction Scheme (III), are available from General Intermediates of Canada, Inc., Edmonton, Alberta, CA (www. generalintermediates.com) and / or Interchim, France (www.interchim.com), or can be prepared using standard techniques. Countless references of texts that show suitable synthetic methods are provided below. Alternatively, the 2,4-pyrimidinediamine compounds of the invention can be prepared from substituted or unsubstituted 4-amino-2-pyrimidinoles as illustrated in the Reaction Scheme (IV), below: Reaction Scheme (IV) 42 (I) In Reaction Scheme (IV), R2, R4, R5, R6, L1 and L2 are as previously defined by the Reaction Scheme (I) and Z represents a leaving group. With reference to the Reaction Scheme (IV), the C2-hydroxyl of 4-amino-2-pyrimidinol 40, is more reactive toward nucleophiles than the amino C4, so that such a reaction with the amine 6 provides 2,4-pyrimidinediamine N2 -substituted 42. Subsequent reaction with compound 44, which includes a good leaving group Z, or amine 10, provides a 2,4-pyrimidinediamine in accordance with the structural formula (I) Compound 44 can include virtually any leaving group which can be displaced by the N2-substituted 2,4-pyrimidinediamine C4 amino 42. Suitable leaving groups Z include, but are not limited to, halogens, methanesulfonyloxy (mesyloxy; "OMs" ), trifluoromethanesulfonyloxy ("OTf") and p-toluenesulfonyloxy (tosyloxy; "OTs"), benzenesulfonyloxy ("besylate"), and methane-benzenesulfonyloxy ("nosylate"). Other suitable leaving groups will be apparent to those skilled in the art. The substituted 4-amino-2-pyrimidinol starting materials can be obtained commercially or synthesized using standard techniques. Countless references of texts that show suitable synthetic methods are provided below. In yet another exemplary embodiment, the compounds 2,4-pyrimidinediamine of the invention can be prepared from 2-chloro-4-aminopyrimidines or 2-amino-4-chloropyrimidines as illustrated in the Reaction Scheme (V), below: Reaction Scheme (V) 54 56 In the Reaction Scheme (V), R2, R4, R5, R6, L1, L2 and X, are as defined for the Reaction Scheme (I) and Z is as defined for the Reaction Scheme (IV). With reference to the Reaction Scheme (V), 2-amino-4-chloropyrimidine 50 is reacted with amino 10, to give unsubstituted 2-pyrimidine 4N-substituted 52, which, after reaction with the compound 31 or amine 6 , provides a 2,4-pyrimidinediamine in accordance with structural formula (I). Alternatively, 2-chloro-4-amino-pyrimidine 54 can be reacted with compound 44, followed by amine 6 to give a compound according to structural formula (I). A variety of pyrimidines 50 and 54 suitable for use as starting materials in Reaction Scheme (V), are commercially available, including by way of example and without limitation, 2-amino-4,6-dichloropyrimidine (Aldrich # A4860- 1; CAS Registry 56-05-3); 2-amino-4-chloro-6-methoxy-pyrimidine (Aldrich # 51,864-6; CAS Registry 5734-64-5); 2-amino-4-chloro-6-methylpyrimidine (Aldrich # 12,288-2; CAS Registry 5600-21-5); and 2-amino-4-chloro-6-methylthiopyrimidine (Aldrich # A4600-5; CAS Registry 1005-38-5). Additional pyrimidine starting materials are available from General Intermediates of Canada, Inc., Edmonton, Alberta, CA (www. Generalintermediates.com) and / or Interchim, France (www.interchim.com), or can be prepared using techniques standards Countless references of texts that show suitable synthetic methods are provided below. Alternatively, 4-chloro-2-pyrimidinamines 50 can be prepared as illustrated in the Reaction Scheme (Va): Diagram of Reaction (Va) 53 51 ArC03H In the Reaction Scheme (Va), R5 and R6 are as previously defined by the structural formula (I). In the Reaction Scheme (Va), dicarbonyl 53 is reacted with guanidine to give 2-pyrimidinamine 51. Reaction with peracids as complexes of m-chloroperbenzoic acid, trifluoroperacetic acid or hydrogen peroxide and urea yields N-oxide 55, which is then halogenated to give 4. -chloro-2-pyrimidinamine 50. The corresponding 4-halo-2-pyrimidinamines can be obtained using suitable halogenation reagents. In yet another exemplary embodiment, the 2,4-pyrimidinediamine compounds of the invention can be prepared from substituted and unsubstituted uridines as illustrated in Reaction Scheme (VI), below: Reaction Scheme (VI) 64 acid-catalyzed deprotection (l) 28 In Reaction Scheme (VI), R2, R4, R5, R6, L1, L2 and X are as previously defined by the Reaction Scheme (I) and the PG exponent represents a protecting group, as discusses in conjunction with the Reaction Scheme (Hb). In accordance with Reaction Scheme (VI), uridine 60 has a reactive center C4, such that reaction with amine 10 or protected amine 21, provides N4-substituted cytidine 62 or 64, respectively. Acid-catalyzed deprotection of N-substituted 62 or 64 (when "PG" represents a labile acid protecting group) provides N4-substituted cytokine 28, which can be subsequently halogenated at the C2 position and reacted with amine 6 to give a 2,4-pyrimidinediamine according to the structural formula (I). The cytidines can also be used as starting materials in an analogous manner, as illustrated in the Reaction Scheme (VII), below: Reaction Scheme (VII) 64 acid-catalyzed deprotection (i) 28 In Reaction Scheme (VII), R2, R4, R5, R6, L1, L2 and X are as previously defined in the Reaction Scheme (I) and the PG exponent represents a protecting group, as discuss above. With reference to Reaction Scheme (VII), such as uridine 60, cytidine 70 has a reactive center C4, such that reaction with amine 10 or protected amine 21, provides N4-substituted cytidine 62 or 64, respectively. These cytidines 62 or 64 are then treated as previously described by the Reaction Scheme (VI) to give a 2,4-pyrimidinediamine in accordance with structural formula (I). Although Reaction Schemes (VI) and (VII) are exemplified with ribosilnucleosides, it will be appreciated by those skilled in the art that the corresponding 2'-deoxyrribo and 2 ', 3' -didesoxyrribo nucleosides, as well as nucleosides including sugars or sugar analogs different than ribose, could also work. Numerous uridines and cytidines useful as starting materials in Reaction Schemes (VI) and (VII) are known in the art and include, by way of example and without limitation, 5-trifluoromethyl-2'-deoxycytidine (Chem. #ABCR F07669; CAS Record 66,384-66-5); 5-bromouridine (Chem. Sources Int'l 2000; CAS Registry 957-75-5); 5-iodo-2'-deoxyuridine (Aldrich # 1-775-6; CAS Registry 54-42-2); 5-fluorouridine (Aldrich # 32,937-1; CAS Registry 316-46-1); 5-iodothyidine (Aldrich # 85,259-7; CAS Registry 1024-99-3); 5- (trifluoromethyl) uridine (Chem. Sources Int'l 2000; CAS Registry 70-00-8); 5-trifluoromethyl-2'-deoxyuridine (Chem. Sources Int'l 2000; CAS Registry 70-00-8). The additional uridines and cytidines which can be used as starting materials in Reaction Schemes (VI) and (VII) are available from General Intermediates of Canada, Inc., Edmonton, Alberta, CA (ww., Generalintermediates.) And / or Interchim, France (www.interchim.com), or can be prepared using standard techniques. Countless references of texts that show suitable synthetic methods are provided below. The 2,4-pyrimidinediamine compounds of the invention can also be synthesized from substituted pyrimidines, such as chloro-substituted pyrimidines, as illustrated in Reaction Schemes (HIV) and (IX), below: Reaction Scheme (HIV) 83 Reaction Scheme (IX) 99 In the Reaction Scheme (HIV) and (IX), R, R4, L1, L2 and Ra are as previously defined by the structural formula (I) and "Ar" represents an aryl group. With reference to the Reaction Scheme (HIV), the reaction of a 2,4,6-trichloropyrimidine 80 (Aldrich # T5, 620-0; CAS # 3764-01-0) with amine 6 provides a mixture of three compounds: mono, di and tri-amines of substituted pyrimidines 81, 82 and 83, which can be separated and isolated using HPLC or other conventional techniques. The mono and diamines 81 and 82 can also be made, react with amines 6 and / or 10, to give 2,4,6-pyrimidinetriamines N2, N4, N6-trisubstituted 84 and 85, respectively. The 2, 4-pyrimidinediamines N2, N4-bis-substituted can be prepared in a manner analogous to the Reaction Scheme (HIV), using 2,4-dichloro-5-methylpyrimidine or 2,4-dichloro-pyrimidine as starting materials. In this case, the mono-substituted pyrimidinamine corresponding to compound 81 is not obtained. Instead, the reaction proceeds to give the 2-pyrimidinediamine N2, N4-bis-substituted directly. With reference to the Reaction Scheme (IX), 2,4,5,6-tetrachloropyrimidine 90 (Aldrich # 24,671-9; CAS # 1780- - 40-1), is reacted with excess of amine 6 to give a mixture of three compounds: 91, 92, and 93, which can be separated and isolated using HPLC or other conventional techniques. As illustrated, 5,6-dichloro-2, 4-pyrimidinediamine N 2, N 4 -bis-substituted 92 can further be reacted at the C 6 halide with, for example, a nucleophilic agent 94 to give the compound 95. Alternatively, the compound 92 can be converted to 5-chloro-6-aryl-2,4-pyrimidinediamine N2, N4-bis-substituted 97, via a Susuki reaction. The 2,4-pyrimidinediamine 95 can be converted to 2,4-pyrimidinediamine 99 by reaction with Bn3SnH. As will be recognized by those skilled in the art, the 2, 4-pyrimidinediamines according to the invention, synthesized via the exemplary methods described above, or by other well-known means, can also be used as starting materials and / or intermediates to synthesize additional 2,4-pyrimidinediamine compounds of the invention. A specific example is illustrated in the Reaction Scheme (X), below: Reaction Scheme (X) 100 104 In the Reaction Scheme (X); R4, R5, Rd, L2 and Ra are as previously defined by the structural formula (I): Each Ra 'is independently a Ra, and may be the same or different from the illustrated Ra. With reference to the Reaction Scheme (X), the carboxylic acid or ester 100, can be converted to the amide 104 by reaction with the amine 102. In the amine 102, Ra 'can be the same or different from the acid or ester Ra 100. Similarly, ester carbonate 106 can be converted to carbamate 108. A second specific example is illustrated in Reaction Scheme (XI), below: Reaction Scheme (XI) In the Reaction Scheme (XI), R4, R5, R6, L2 and Rc are as previously defined by the structural formula (I). With reference to the Reaction Scheme (XI), the amide 110 or 116 can be converted to the amine 114 or 118, respectively, by borane reduction with borane methylsulfide complex 112. Other reactions suitable for synthesizing 2,4-pyrimidinediamine compounds from 2, 4-pyrimidinediamine starting materials will be apparent to those of skill in the art. Although many of the synthetic schemes discussed above do not illustrate the use of protecting groups, those skilled in the art will recognize that in some cases, the substituents R2, R4, R5, R6, L1 and / or L2 may include functional groups that require protection. The exact identity of the protecting group used will depend, among other things, on the identity of the functional group to be protected and the reaction conditions used in the particular synthetic scheme, and will be apparent to those skilled in the art. The guide for selecting protective and chemical groups for attachment and removal suitable for a particular application can be found, for example, in Greene & Wuts, supra. Prodrugs according to structural formula (II) can be prepared by routine modification of the methods described above. Alternatively, such prodrugs can be prepared by reacting a suitably protected 2-pyrimidinediamine of structural formula (I) with a suitable progroup. Conditions for carrying out such reactions and for deprotecting the product to give a prodrug of formula (II) are well known. Numerous references that show useful methods for synthesizing pyrimidines in a general manner, as well as also starting materials described in Reaction Schemes (I) - (IX), are well known in the art. For specific guidance, the reader is referred to Brown, DJ, "The Pyrimidines," in The Chemistry of Heterocyclic Compounds, Volume 1 6 (Weissberger, A., Ed.), 1962, Interscience Publishers, (A Division of John Wiley & amp; amp;; Sons), New York ("Brown I"); Brown, DJ, "The Pyrimidines", in The Chemistry of Heterocyclic Compounds, Volume 16, Supplement I (Weissberger, A. and Taylor, E.C., Ed.), 1970, Wiley-Interscience, (A Division of John Wiley & amp; amp; Sons), New York (Brown II "), Brown, DJ," The Pyrimidines ", in The Chemistry of Heterocyclic Compounds, Volume 16, Supplement II (Weissberger, A. and Taylor, E. C, Ed.), 1985 , An ínterscience Publication (John Wiley &Sons), New York ("Brown III"), Brown, DJ, "The Pyrimidines" in The Chemistry of Heterocyclic Compounds, Volume 52 (Weissberger, A. and Taylor, E. C, Ed.), 1994, John Wiley &Sons, Inc., New York, pp. 1-1509 (Brown IV "); Kenner, G. W. and Todd, A., in Heterocyclic Compounds, Volume 6, (Elderfield, R. C, Ed.), 1957, John Wiley, New York, Chapter 7 (pyrimidines); Paquette, L.A., Principles of Modern Heterocyclic Chemistry, 1968, W. A. Benjamin, Inc., New York, pp. 1-401 (uracil synthesis pp. 313, 315; pyrimidine synthesis pp. 313-316; amino pyrimidine synthesis pp. 315); Joule, J.A., Mills, K. and Smith, G.F., Heterocyclic Chemistry, 3rd Edition, 1995, Chapman and Hall, London, UK, p. 1-516; Vorbrüggen, H. and Ruh-Pohlenz, C, Handbook of Nucleoside Synthesis, John Wiley & amp; amp;; Sons, New York, 2001, pp. 1-631 (protection of pyrimidines by acylation pp. 90-91; silylation of pyrimidines pp. 91-93); Joule, J.A., Mills, K. and Smith, G.F., Heterocyclic Chemistry, 4th Edition, 2000, Blackwell Science, Ltd, Oxford, UK, p. 1-589; and Comprehensive Organic Synthesis, Volume 1-9 (Trost, B. M. and Fleming, I., Ed.), 1991, Pergamon Press, Oxford, UK. It should be understood by those skilled in the art, that in Reaction Schemes I through XI, nitrogen N4 can be substituted for R4c as described throughout the specification and in the examples provided herein.

Inhibition of Signal Cascades of the Fc Receiver The active 2,4-pyrimidinediamine compounds of the invention inhibit receptor signaling cascades Fc that lead, among other things, to the degranulation of cells. As a specific example, the compounds inhibit the FceRI and / or Fc? RI signal cascades, which lead to the degranulation of immune cells such as neutrophil, eosinophil, mast and / or basophil cells. Both mast and basophil cells play a central role in allergen-induced disorders, including, for example, allergic rhinitis and plasma. With reference to Figure 1, after exposure to allergens, which may be, among other things, pollen or parasites, IgE antibodies specific for the allergen are synthesized by B cells activated by IL-4 (or IL-3) and others. messengers to interrupt the synthesis of specific antibodies of the IgE class. These allergen specific IgE bind to high affinity FceRI. After binding of the antigen, the FceRIs bound to IgE are cross-linked and the signal transduction path of the IgE receptor is activated, which leads to degranulation of the cells and consequent release and / or synthesis of a host of chemical mediators, which include histamine, proteases (e.g., tryptase and chymase), lipid mediators such as leukotrienes (e.g., LTC4), platelet activating factor (PAF) and prostaglandins (e.g., PGD2) and a series of cytokines, which include TNF-α, IL-4, IL-13, IL-5, IL-6, IL-8, GMCSF, VEGF and TGF-β. The release and / or synthesis of these mediators from mast cells and / or basophils accounts for the early and late stage responses induced by allergens, and is directly linked to downstream events that lead to a sustained inflammatory state. Molecular events in the FceRI signal transduction path leading to the release of preformed mediators via degranulation and release and / or synthesis of other chemical mediators are well known and are illustrated in Figure 2. With reference to Figure 2, FceRI is a heterotetrameric receptor composed of an alpha subunit, a beta subunit and two gamma subunits (gamma homodimer), which bind to IgE. The cross-linking of FceRI linked to IgE by multivalent binding agents (including, for example, IgE-specific allergens or antibodies or anti-IgE fragments), induces the association and rapid activation of the Lyn kinase related to Src. The activation portions based on the tyrosine immunoreceptor (ITAMS) phosphorylate Lyn in the beta and gamma intracellular subunits, which lead to the recruitment of additional Lyn to the beta subunit and Syk kinase to the gamma homodimer. These kinases associated with the receptor, which are activated via intra- and intermolecular phosphorylation, phosphorylate other components of the pathway, such as the Btk kinase, LAT, and phospholipase C-gamma PLC-gamma). The activated PLC-gamma initiates the trajectories that lead to the activation of protein kinase C and Ca2 + immobilization, both of which are required for degranulation. FceRI crosslinking also activates the three major classes of mitogen-activated protein kinases (MAP), ie, ERK 1/2, JNK 1/2 and p38. The activation of these trajectories is important in the transcriptional regulation of proinflammatory mediators, such as TNF-a and IL-6, as well as leucotriene mediator lipid CA (LTC4). Although not illustrated, the Fc? RI signaling cascade is believed to carry some common elements with the FceRI signaling cascade. Importantly, like FceRI, Fc? RI includes a gamma homodimer that is phosphorylated and recruits Syk, and like FceRI, activation of the Fc? RI signaling cascade leads, among other things, to degranulation. Other Fc receptors carrying the gamma homodimer, and which can be regulated by the compounds 2, Active 4-pyrimidinediamine, include but are not limited to, FceRI and Fc? RI. The ability of the 2,4-pyrimidinediamine compounds of the invention to inhibit signaling cascades of the Fc receptor can be simply determined or confirmed in in vitro assays. Suitable assays to confirm the inhibition of FceRI-mediated degranulation are given in the Examples section. In a typical assay, cells capable of undergoing FceRI-mediated degranulation, such as mast cells or basophils, are first grown in the presence of IL-4, Stem Cell Factor (SCF), IL-6 and IgE, to increase the expression of FceRI, exposed to a test compound 2, 4-pyrimidinediamine of the invention, and stimulated with anti-IgE antibodies (or, alternatively, an IgE-specific allergen). After incubation, the amount of a chemical mediator and another chemical agent released and / or synthesized as a consequence of activation of the FceRI signaling cascade, can be quantified using standard techniques and compared to the amount of mediator or agent released from of control cells (ie, cells that are stimulated but not exposed to the test compound). The concentration of the test compound that provides a 50% reduction in the amount of mediator or agent measured, compared to the control cells, is the IC50 of the test compound. The origin of the mast or basophil cells used in the assay will depend, in part, on the intended use for the compounds and will be apparent to those skilled in the art. For example, if the compounds will be used to treat or prevent a particular disease in humans, a convenient source of mast cells or basophils is a human or other animal, which constitutes an accepted or known clinical model for the particular disease. Thus, depending on the particular application, the mast cells or basophils may be derived from a wide variety of animal sources, ranging from for example, lower mammals such as mice and rats, to dogs, sheep and other mammals commonly used in clinical tests, even higher mammals such as monkeys, chimpanzees and monkeys to humans. Specific examples of cells suitable for carrying out in vitro assays include, but are not limited to, basophilic cells from rodents or humans, basophilic leukemia cell lines in rat, mast cells in primary mice (such as mouse mast cells derived from of bone marrow "BMMC") and primary human mast cells isolated from umbilical cord blood ("CHMC") or other tissues such as lung. Methods for isolating and culturing these cell types are well known and are provided in the Examples section (see for example, Demo et al., 1999, Cytometry 36 (4): 340-348 and co-pending application Series No. 10 / 053,355, filed on November 8, 2001, descriptions of which are incorporated herein by reference). Of course, other types of immune cells that degranulate after activation of the FceRI signaling cascade can also be used, including for example, eosinophils. As will be recognized by those skilled in the art, the quantified agent or mediator is not critical. The only requirement is that it be a mediator or agent released and / or synthesized as a consequence of indicating or activating the signaling cascade of the Fc receptor. For example, with reference to Figure 1, activation of the FceRI signaling cascade in mast cells and / or basophils leads to numerous downstream events. For example, activation of the FceRI signaling cascade leads to immediate release (e.g., within 1-3 minutes after receptor activation) of a variety of preformed mediators and chemical agents via degranulation. In this way, in a modality, the mediator or quantified agent may be specific to the granules (ie, present in granules but not in the cytoplasm of the cell, generally). Examples of granule-specific mediators or agents that can be quantitated to determine and / or confirm the activity of a 2-pyrimidinediamine compound of the invention include, but are not limited to, granule specific enzymes such as hexosaminidase and tryptase and specific components of the granule, such as histamine and serotonin. Assays to quantify such factors are well known, and in many cases, are commercially available. For example, the triptase and / or hexosaminidase released can be quantified by incubating the cells with unfolding substrates that are fluorescent after cleavage and quantifying the amount of fluorescence produced using conventional techniques. Such fluorogenic substrates which can be split are commercially available. For example, fluorogenic substrates Z-Gly-Pro-Arg-AMC (Z = benzyloxycarbonyl; AMC = 7-amino-4-methylcoumarin; BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA 19462, Catalog No. P-142) and Z-Ala-Lys-Arg-AMC (Enzyme Systems Products, a division of ICN Biomedicals, Inc., Livermore, CA 94550, Catalog No. AMC-246), can be used to quantify the amount of tryptase supplied. The fluorogenic substrate 4-methylumbelliferyl-N-acetyl-β-D-glucosaminide (Sigma, St. Louis, MO, Catalog # 69585), can be used to quantitate the amount of hexosaminidase releases. Released histamine can be quantified using a commercially available enzyme-linked immunosorbent assay (ELISA), such as Immunotech # IM2015 histamine ELISA assay (Beckman-Coulter, Inc.). Specific methods for quantifying the release of tryptase, hexosaminidase and histamine, are provided in the Examples section. Any of these assays can be used to determine or confirm the activity of the 2-pyrimidinediamine compounds of the invention. Referring again to Figure 1, degranulation is only one of several responses initiated by the FceRI signaling cascade. In addition, activation of this signaling pathway leads to de novo synthesis and release of cytokines and chemokines such as IL-4, IL-5, IL-6, TNF-a, IL-13 and lPl-a), and release of lipid mediators such as leukotrienes (for example, LTC4), platelet activation factor (PAF) and prostaglandins. Accordingly, the 2,4-pyrimidinediamine compounds of the invention can also be titrated by activity, quantifying the amount of one or more of these mediators released and / or synthesized by active cells. Other than the specific components of the granule discussed above, these "late stage" mediators are not released immediately after activation of the FceRI signaling cascade. Therefore, when these late stage mediators are quantified, care must be taken to ensure that the activated cell culture is incubated for a sufficient time to result in the synthesis (if necessary) and release of the mediator to be quantified. In general, PAF mediators and lipids such as leukotriene C4 are released 3-30 minutes after the activation of FceRI. Cytokines and other late stage mediators are released approximately 4-8 hours after the activation of FceRI. The incubation times suitable for a specific mediator will be apparent to those of skill in the art. The specific guidance and trials are provided in the Examples section. The amount of a particular late stage mediator, released, can be quantified using any standard technique. In one embodiment, the quantity (s) can be quantified using ELISA assays. ELISA test kits suitable for quantifying the amount of TNF-cc, IL-4, IL-5, IL-6 and / or IL-13 released, is available from, for example, Biosource International, Inc., Camarillo, CA 93012 (see for example, Catalogs Nos. KHC3011, KHC0042, KHC0052, KHC0061 and KHC0132). ELISA test kits suitable for quantifying the amount of leukotriene C4 (LTC4) released from cells are available from Cayman Chemical Co., Ann Arbor, MI 48108 (see for example, Catalog No. 520211). Typically, the active 2,4-pyrimidinediamine compounds of the invention will exhibit IC50 with respect to the degranulation mediated by FceRI and / or mediator released or synthesis of approximately 20 μM or less, measured in an in vitro assay, such as one of the in vitro assays described above or in the Examples section. Of course, those skilled in the art will appreciate that compounds which have lower IC 50's, for example, in the order of 10 μM, 1 μM, 100 nM, 10 nM, 1 nM, or even lower, are particularly useful. Experts in the art will also appreciate that the various mediators discussed above may induce different adverse effects or present different potencies with respect to the same adverse effect. For example, the lipid mediator LTC4 is a potent vasoconstrictor - it is approximately 1000 times more potent inducing vasoconstriction than histamine. As another example, in addition to mediating atopic or Type I hypersensitivity reactions, cytokines can also cause tissue remodeling and cell proliferation. Thus, although compounds which inhibit the release and / or synthesis of any of the chemical mediators previously discussed are useful, those skilled in the art will appreciate that the compounds which inhibit the release and / or synthesis of a plurality, or even if all mediators previously described find particular use, such compounds are useful for improving or avoiding altogether, a plurality, or even all the adverse effects induced by particular mediators. For example, compounds which inhibit the release of the three types of mediators - granule specific, lipids and cytokines - are useful for treating or preventing immediate Type I hypersensitivity reactions, as well as the associated chronic symptoms along with these. The compounds of the invention capable of inhibiting the release of more than one type of mediator (eg, granule specific or late stage), can be identified by determining the IC50 with respect to a representative mediator of each class using the various assays in vi described above (or other equivalent in vitro tests). The compounds of the invention which are capable of inhibiting the release of more than one type of mediator will typically present an IC 50 for each type of mediator tested of less than about 20 μM. For example, a compound which has an IC50 of 1 μM with respect to the released histamine (IC50histamine) and an IC50 of 1 nM with respect to the synthesis and / or release of leukotriene LTC4 (ICso1,104), inhibits both the release of the late stage mediator as immediate (specific to the granule). As another specific example, a compound having a IC50triptase of 10 μM, an IC5o1TC4 of 1 μM and a IC50IL "4 of 1 μM, inhibits the release of the immediate mediator (granule specific), lipid and cytokine. using the IC50 of a representative mediator of each class, those skilled in the art will appreciate that the IC50 of a plurality, or even of all the mediators comprising one or more of the classes, can be obtained.The amount (s) and identity (s) of mediators for which the IC50 data should be assessed by a particular compound and the application, will be apparent to those skilled in the art.Similar assays can be used to confirm the inhibition of signal transduction cascades initiated by other Fc receptors, such as FcaRI, Fc? RI and / or Fc? RIII signaling, with routine modification, for example, the ability of the compounds to inhibit transduction of the Fc? RI signal can be confirmed in assays similar to those described above, with the exception that the Fc? RI signaling cascade is activated, for example, by incubating the cells with IgG and an allergen or IgG specific antibody, instead of IgE and an allergen or IgE-specific antibody. Suitable cell types, activating agents and quantifying agents to confirm the inhibition of other Fc receptors, such as Fc receptors comprising a gamma homodimer, will be apparent to those skilled in the art. A particularly useful class of compounds includes those 2-pyrimidinediamine compounds that inhibit the release of immediate granule-specific mediators and late stage mediators, with approximately equivalent IC 50. By approximately equivalent, it means that the IC50 for each type of mediator is within approximately a 10-fold interval of another. Another particularly useful class of compounds includes those 2,4-pyrimidinediamine compounds that inhibit the release of immediate granule-specific mediators., mediators lipids and mediators of cytokine with IC50 approximately equivalent. In a specific embodiment, such compounds inhibit the release of the following mediators with approximately equivalent IC50: histamine, tryptase, hexosaminidase, IL-4, IL-5, IL-β, IL-13, TNFa and LTC4. Such compounds are particularly useful for, among other things, alleviating or avoiding altogether, both the late and early stage responses associated with the atopic or immediate Type I hypersensitivity reactions. Ideally, the ability to inhibit the release of all desired types of mediators will reside in a single compound. However, mixtures of compounds can also be identified, which achieve the same result. For example, a first compound which inhibits the release of granule-specific mediators can be used in combination with a second compound which inhibits the release and / or synthesis of cytokine mediators. In addition to the degranulation trajectories of FceRI or Fc? RI discussed above, the degranulation of mast and / or basophil cells can be induced by other agents. For example, ionomycin, a calcium ionophore that derives the cell machinery of FceRI signal transduction or early Fc? RI, directly induces a calcium flux that activates degranulation. With reference again to Figure 2, the PLC? activated, initiates trajectories that lead to, among other things, mobilization of calcium ions and subsequent degranulation. As illustrated, this Ca2 + mobilization is then activated in the FceRI signal transduction path. As mentioned above, and as illustrated in Figure 3, ionomycin directly induces Ca + mobilization and a Ca2 + flux that leads to degranulation. Other ionophores that induce degranulation in this manner include A23187. The ability of ionophores to induce granulation, such as ionomycin to derive the late stages of the FceRI and / or FcRI signaling cascades, can be used as a countable display to identify active compounds of the invention, which specifically exert their activity inhibitory-degranulation, blocking or inhibiting the signaling cascades FceRI or Fc? RI early, as discussed above. Compounds that specifically inhibit such early FceRI or Fc? RI-mediated degranulation not only inhibit degranulation and rapid subsequent release of histamine, tryptase and other granule contents, but also inhibit the pro-inflammatory activation pathways that cause the release of TNFa, IL-4, IL-13 and lipid mediators such as LTC4. Thus, compounds which specifically inhibit such early FceRI and / or Fc? RI-mediated degranulation, block or inhibit not only acute atopic or Type I hypersensitivity reactions, but also late responses involving multiple inflammatory mediators. Compounds of the invention that specifically inhibit the degranulation mediated by FceRI and / or Fc? RI early, are those compounds that inhibit degranulation mediated by FceRI and / or Fc? RI (for example, have an IC50 of less than about 20 μM; with respect to the release of a mediator or specific component of the granule, as measured in an in vitro assay, with cells stimulated with an IgE or IgG binding agent), but which do not appreciably inhibit the degranulation induced by ionophers. In one embodiment, the compounds are considered to not appreciably inhibit ionomer-induced degranulation if they exhibit an IC50 of ionophore-induced degranulation greater than about 20 μM, as measured in an in vitro assay. Of course, active compounds that still exhibit IC50 of ionophore-induced degranulation, or that do not inhibit ionophore-induced degranulation, are particularly useful. In another embodiment, the compounds are considered to not appreciably inhibit degranulation induced by ionophers if they present more than 10-fold difference in their IC50 of degranulation mediated by FceRI and / or Fc? RI and ionophore-induced degranulation, as measured in a in vitro assay. Suitable assays for determining the IC50 of ionophore-induced degranulation include any of the degranulation assays previously described, with the modification that the cells are stimulated or activated with a calcium ionomer that induces degranulation, such as ionomycin or A23187 (AG Scientific , San Diego, CA), instead of anti-IgE antibodies or an IgE-specific allergen. Specific assays to assess the ability of a particular 2,4-pyrimidinediamine compound of the invention to inhibit ionophore-induced degranulation are given in the Examples section. As will be recognized by those skilled in the art, compounds that exhibit a high degree of FceRI-mediated degranulation selectivity find particular use as such compounds selectively targeted to the FceRl cascade and which do not interfere with other degranulation mechanisms. Similarly, compounds that exhibit a high degree of FcγRI-mediated degranulation selectivity find particular use as such compounds selectively targeted to the FcγRI cascade and which do not interfere with other degranulation mechanisms. The compounds which exhibit a high degree of selectivity are generally 10 times or more selective for FceRI or Fc? RI-mediated degranulation on ionophore-induced degranulation, such as ionomycin-induced degranulation. Accordingly, the activity of the 2,4-pyrimidinediamine compounds of the invention can also be confirmed in biochemical or cellular assays of Syk kinase activity. Referring again to Figure 2, in the FcγRl signaling cascade in mast and / or basophil cells, the Syk kinase phosphorylates LAT and PLC-gamal, which lead to, among other things, degranulation. Any of these activities can be used to confirm the activity of the 2,4-pyrimidinediamine compounds of the invention. In one embodiment, the activity is confirmed by contacting an isolated Syk kinase, or an active fragment thereof, with a 2,4-pyrimidinediamine compound in the presence of a Syk kinase substrate (eg, a synthetic peptide or a protein). which is known to be phosphorylated by Syk in a signaling cascade) and assess whether the Syk kinase phosphorylates the substrate. Alternatively, the assay can be carried out with the cells expressing a Syk kinase. Cells can express Syk kinase endogenously or can be engineered to express a recombinant Syk kinase. The cells can optionally also express the Syk kinase substrate. Cells suitable for performing such confirmatory assays, as well as methods for engineering appropriate cells, will be apparent to those skilled in the art. Specific examples of suitable biochemical and cellular assays to confirm the activity of 2,4-pyrimidinediamine compounds, are provided in the Examples section. Generally, compounds that are inhibitors of Syk kinase will present an IC50 with respect to the activity of Syk kinase, such as the ability of Syk kinase to phosphorylate a synthetic or endogenous substrate, in a cell or in vitro assay , in the range of approximately 20 μM or less. Experts in the art will appreciate that compounds having lower IC 50's, such as in the range of 10 μM, 1 μM, 100 nM, 10 nM, 1 nM, or even lower, are particularly useful.

Uses and Compositions As discussed previously, the active compounds of the invention inhibit the signaling cascade of the Fc receptor, especially those Fc receptors that include a gamma homodimer, such as the FceRI and / or Fc? RI signaling cascades, leading to , among other things, the release and / or synthesis of chemical mediators from cells, either via degranulation and other processes. As is also discussed, the active compounds are also potent inhibitors of the Syk kinase. As a consequence of these activities, the active compounds of the invention can be used in a variety of in vitro, in vivo and ex vivo contexts, to regulate or inhibit the Syk kinase signaling cascades, in which, the Syk kinase plays a paper, signaling cascades of the Fc receptor and the biological responses made by such signaling cascades. For example, in one embodiment, the compounds can be used to inhibit Syk kinase, either in vitro or in vivo, in virtually any cell type that expresses the Syk kinase. They can also be used to regulate signal transduction cascades, in which Syk kinase plays a role. Such Syk-dependent signal transduction cascades include, but are not limited to, the signal transduction cascades of FceRI, Fc? RI, Fc? RIII, BCR and integrin. The compounds can also be used in vitro or in vivo, to regulate, and in particular, inhibit the cellular or biological responses effected by such Syk-dependent signal transduction cascades. Such cellular or biological responses include, but are not limited to, respiratory burst, cell adhesion, cellular degranulation, cellular distribution, cell migration, cellular aggregation, phagocytosis, cytokine synthesis and release, cell maturation and Ca2 + flux. Importantly, the compounds can be used to inhibit Syk kinase in vivo as a therapeutic method towards the treatment or prevention of diseases mediated, either completely or in part, by a Syk kinase activity. Non-limiting examples of diseases mediated by Syk kinase that can be treated or prevented with the compounds, are those discussed in more detail below. In another embodiment, the active compounds can be used to regulate or inhibit Fc receptor signaling cascades and / or FceRI-mediated degranulation and / or FcγRI as a therapeutic procedure towards the treatment or prevention of diseases characterized by, caused by and / or associated with the release or synthesis of chemical mediators, such as signaling cascades of the Fc receptor or degranulation. Such treatments can be administered to animals in veterinary contexts or to humans. Diseases which are characterized by, caused by or associated with such mediator releasers, synthesis or degranulation, and which may therefore be treated or prevented with the active compounds, include by way of example and without limitation, allergic reactions or anaphylactic hypersensitivity or atopy, allergy (eg, allergic conjunctivitis, allergic rhinitis, atopic asthma, atopic dermatitis and food allergies), low grade scars (eg, scleroderma, increased fibrosis, keloids, post-surgical scars, pulmonary fibrosis, vascular spasms, migraine, reperfusion injury, and post-myocardial infarction), diseases associated with tissue destruction (eg, COPD, cardiobronchitis, and post-myocardial infarction), diseases associated with tissue inflammation (eg, inflammatory bowel syndrome, " spastic colon and inflammatory bowel disease), inflammation and scarring. the innumerable diseases discussed above, empirical animal and cellular data confirm that the 2-pyrimidinediamine compounds described herein are also useful for the treatment or prevention of autoimmune diseases, as well as the various symptoms associated with such diseases. The types of autoimmune diseases that can be treated or prevented with the 2,4-pyrimidinediamine compounds generally include those disorders that involve tissue injury that occurs as a result of the cell-mediated and / or humoral response to immunogens or antigens of endogenous and / or exogenous origin. Such diseases are frequently referred to as diseases involving non-anaphylactic hypersensitivity reactions (ie, Type II, Type III and / or Type IV). As discussed previously, Type I hypersensitivity reactions result, in general, from the release of pharmacologically active substances, such as histamine, from mast cells and / or basophils after contact with a specific exogenous antigen. As mentioned above, such Type I reactions play a role in numerous diseases, including allergic asthma, allergic rhinitis, etc. Type II hypersensitivity reactions (also referred to as cytotoxic, complement-dependent cytolytic or cell-stimulating hypersensitivity reactions) result when immunoglobulins react with antigenic components of cells or tissues, or with an antigen or hapten that has become intimately coupled to cells or tissues. Diseases that are commonly associated with Type II hypersensitivity reactions include, but are not limited to, autoimmune hemolytic anemia, fetal erythroblastosis, and Good Shepherd disease. Type III hypersensitivity reactions (also referred to as toxic complex, soluble complex, or hypersensitivity reactions of immune complexes), result from the deposition of circulating antigen-immunoglobulin complexes soluble in spleens or tissues, with acute inflammatory reactions companions at the site of immune complex deposition. Non-limiting examples of prototype Type III reaction diseases include, the Arthus reaction, rheumatoid arthritis, serum malignancy, systemic lupus erythematosus, certain types of glomerulonephritis, multiple sclerosis, and pemphigoid bolus. Type IV hypersensitivity reactions (often called cell-mediated, delayed, or tuberculin-mediated hypersensitivity reactions) are caused by sensitized T-lymphocytes, which result from contact with a specific antigen. Non-limiting examples of diseases cited for involving Type IV reactions are contact dermatitis and allograft rejection. Autoimmune diseases associated with any of the above non-anaphylactic hypersensitivity reactions can be treated or prevented with the 2,4-pyrimidinediamine compounds of the invention. In particular, the methods can be used to treat or prevent those autoimmune diseases frequently characterized as single cell or single organ autoimmune disorders, including but not limited to: Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, Good Shepherd disease, autoimmune thrombocytopenia, sympathetic ophthalmia, myasthenia gravis, Grave's disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy, as well as those autoimmune diseases frequently characterized by autoimmune disorders. systemic, which include, but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis, and pemphigoid bol bear. It will be appreciated by those skilled in the art that many of the autoimmune diseases listed above are associated with severe symptoms, the improvement of which provides significant therapeutic benefit even in cases where the fundamental autoimmune disease can not be improved. Many of these symptoms, as well as their fundamental disease states, result as a consequence of the activation of the Fc? RI signaling cascade in monocyte cells. As the 2,4-pyrimidinediamine compounds described herein, are potent inhibitors of such FcγRI signaling in monocytes and other cells, the methods find use in the treatment and / or prevention of innumerable adverse symptoms associated with the autoimmune diseases listed above. . As a specific example, rheumatoid arthritis (RA) typically results in swelling, pain, loss of movement and tenderness of the target joints throughout the body. RA is characterized by the chronically inflamed synovium that is densely disseminated with lymphocytes. The synovial membrane, which is typically a thick cell layer, becomes intensely cellular and assumes a shape similar to the lymphoid tissue, which includes dendritic cells, T, B and NK cells, macrophages and clusters of plasma cells. This process, as well as a plethora of immunopathological mechanisms that include the formation of antigen-immunoglobulin complexes, eventually result in the destruction of the integrity of the joint, resulting in deformity, permanent loss of function and / or bone erosion. in or near the joint. The methods can be used to treat or improve any, several or all of the symptoms of RA. Thus, in the context of RA, the methods are considered to provide therapeutic benefit (discussed more generally, infra), when a reduction or improvement of any of the symptoms commonly associated with RA is achieved, with respect to whether the treatment results in a concomitant treatment of the RA and / or a reduction in the amount of the factor rheumatoid circulation ("RF"). As another specific example, systemic lupus erythematosus ("SLE") is typically associated with symptoms such as fever, joint pain (arthralgia), arthritis, and serositis (pleurisy or pericarditis). In the context of SLE, the methods are considered to provide therapeutic benefit when a reduction or improvement of any of the symptoms commonly associated with SLE is achieved, with respect to whether the treatment results in a concomitant treatment of the essential SLE. As another specific example, multiple sclerosis ("MS") incapacitates the patient by altering visual acuity; stimulating double vision; altering motor functions affecting walking and use of hands; producing bowel and bladder incontinence; spasticity; and sensory deficiencies (sensitivity to touch, pain and temperature). In the context of MS, the methods are considered to provide therapeutic benefit, when an improvement or reduction in the progress of any or more of the disabling effects commonly associated with the MS is achieved, with respect to whether the treatment results in a treatment. concomitant of the fundamental MS. When used to treat or prevent such diseases, the active compounds may be administered alone, as mixtures of one or more active compounds, or in admixture or combination with other agents useful for treating such diseases and / or the symptoms associated with such diseases. The active compounds can also be administered in admixture or in combination with agents useful for treating other disorders or diseases, such as steroids, membrane stabilizers, 5L0 inhibitors, leukotriene synthesis and receptor inhibitors, IgE isotype inhibitors of disruption or synthesis. of IgE, IgG isotype of interruption or IgG synthesis, β-agonists, tryptase inhibitors, aspirin, COX inhibitors, methotrexate, anti-TNF drugs, retuxin, PD4 inhibitors, p38 inhibitors, PDE4 inhibitors, and antihistamines, to name a few . The active compounds may be administered per se in the form of prodrugs or as pharmaceutical compositions, comprising an active compound or prodrug. Pharmaceutical compositions comprising the active compounds of the invention (or prodrugs thereof), can be manufactured by means of conventional mixing, dissolving, granulating, levigating processes made of confections, emulsifiers, encapsulants, entrapments or lyophilization. The compositions can be formulated in a conventional manner using one or more physiologically suitable carriers, diluents, excipients or auxiliaries., which facilitate the processing of the active compounds in preparations which can be used pharmaceutically. The active compound or prodrug can be formulated into the pharmaceutical compositions per se, or in the form of a hydrate, solvate, N-oxide or pharmaceutically acceptable salt, as previously described. Typically, such salts are more soluble in aqueous solutions than the corresponding free acids and bases, but salts having lower solubility than the corresponding free acids and bases can also be formed. The pharmaceutical compositions of the invention can take a suitable form for virtually any mode of administration including, for example, topical, ocular, oral, buccal, systemic, nasal, injection, transdermal, rectal, vaginal, etc., or a suitable form for administration by inhalation or insufflation. For topical administration, the active compound (s) or prodrug (s) can be formulated with solutions, gels, ointments, creams, suspensions, etc., as are well known in the art. Systemic formulations include those designated for administration by injection, for example, subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as those designated for transdermal, transmucosal oral or pulmonary administration. Useful injectable preparations include sterile suspensions, solutions or emulsions of the active compound (s) in aqueous or oily vehicles. The compositions may also contain formulating agents, such as suspending, stabilizing and / or dispersing agents. Formulations for injection may be presented in unit dosage form, for example, in ampules or in multi-dose containers and may contain added condoms. Alternatively, the injectable formulation may be provided in powder form for reconstitution with a suitable vehicle, including but not limited to, sterile, pyrogen-free water, buffer, dextrose solution, etc., before use. In this case, the active compound (s) can be dried by any known technique, such as lyophilization and reconstituted prior to use. For transmucosal administration, the appropriate penetrants to the barrier to be permeated are used in the formulation. Such penetrants are known in the art. For oral administration, the pharmaceutical compositions may take the form of, for example, tablets, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients, such as binding agents (eg, pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropylmethylcellulose).; fillers (for example, lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (for example, magnesium stearate, talc or silica); disintegrants (e.g., corn starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate). The tablets may be coated by methods well known in the art with, for example, sugars, films or enteric coatings. Liquid preparations for oral administration may take the form of, for example, elixirs, solutions, syrups or suspensions, or they may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (eg, sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (for example, lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, cremophore ™, or fractionated vegetable oils); and preservatives (for example, methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, preservatives, flavors, colorants and sweeteners as appropriate. Preparations for oral administration can be suitably formulated to give controlled release of the active compound or prodrug, as is well known. For buccal administration, the compositions may take the form of tablets or lozenges formulated in a conventional manner. For rectal and vaginal administration routes, the active compound (s) can be formulated as solutions (for retention enemas), suppositories or ointments containing conventional suppository bases, such as cocoa butter or other glycerides . For nasal administration or administration by inhalation or insufflation, the active compound (s) or prodrug (s) can be conveniently delivered in the form of an aerosol atomizer from pressurized packets or a nebulizer, with the use of a suitable propellant, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to supply a measured quantity. Capsules and cartridges for use in an inhaler or insufflator (e.g., capsules and cartridges comprised of gelatin), may be formulated containing a powder mixture of the compound and a suitable powder base, such as lactose or starch. A specific example of an aqueous suspension formulation suitable for nasal administration using commercially available nasal spray devices includes the following ingredients: compound or active prodrug (0.5-20 mg / ml); benzalkonium chloride (0.1-0.2 mg / mL); polysorbate 80 (TWEEN® 80; 0.5-5 mg / ml); sodium carboxymethyl cellulose or microcrystalline cellulose (1- 15 mg / ml); phenylethanol (1-4 mg / ml); and dextrose (20-50 mg / ml). The pH of the final suspension can be adjusted to vary from about pH 5 to pH 7, with a pH of about pH 5.5 being typical. Another specific example of an aqueous suspension suitable for administration of the compounds via inhalation, and in particular for such administration of a compound of the invention, contains 1-20 mg / mL of the compound or prodrug, 0.1-1% (v / v) of Polysorbate 80 (TWEENO80), 50 mM citrate and / or 0.9% sodium chloride. For ocular administration, the active compound (s) or prodrug (s) can be formulated as a solution, emulsion, suspension, etc., suitable for administration to the eye. A variety of vehicles suitable for administering the compounds to the eye are known in the art. Specific non-limiting examples are described in U.S. Patent No. 6,261,547; U.S. Patent No. 6,197,934; U.S. Patent No. 6,056,950; U.S. Patent No. 5,800,807; U.S. Patent No. 5,776,445; U.S. Patent No. 5,698,219; U.S. Patent No. 5,521,222; U.S. Patent No. 5,403,841; U.S. Patent No. 5,077,033; U.S. Patent No. 4,882,150; and U.S. Patent No. 4,738,851. For prolonged supply, the active compound (s) or pro-active ingredient (s) can be formulated. as a depot preparation for administration by implantation or intramuscular injection. The active ingredient can be formulated with suitable polymeric or hydrophobic materials (for example, as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. Alternatively, transdermal delivery systems manufactured as a disc or adhesive patch can be used which slowly release the active compound (s) for percutaneous absorption. In this case, the permeation enhancers can be used to facilitate the transdermal penetration of the active compound (s). Suitable transdermal patches are described in for example, U.S. Patent No. 5,407,713; U.S. Patent No. 5,352,456; U.S. Patent No. 5,332,213; U.S. Patent No. 5,336,168; U.S. Patent No. 5,290,561; U.S. Patent No. 5,254,346; U.S. Patent No. 5,164,189; U.S. Patent No. 5,163,899; U.S. Patent No. 5,088,977; U.S. Patent No. 5,087,240; U.S. Patent No. 5,008,110; and U.S. Patent No. 4,921,475. Alternatively, other pharmaceutical delivery systems may be employed. Liposomes and emulsions are well known examples of delivery vehicles that can be used to deliver active compound (s) or drug (s). Certain organic solvents such as dimethylsulfoxide (DMSO) can also be used, although usually at a higher toxicity cost. The pharmaceutical compositions may, if desired, be presented in a packet or dispensing device, which may contain one or more unit dosage forms containing the active compound (s). The package may, for example, comprise plastic or metal sheets, such as a blister pack or blister pack. The package or dispensing device can be accompanied by instructions for administration.

Effective Dosages The active compound (s) or prodrug (s) of the invention, or compositions thereof, will be used generally, in an effective amount to achieve the proposed result, for example, in an effective amount for Treat or prevent the disease to be treated. The compound (s) can be administered therapeutically to achieve the therapeutic or prophylactic benefit to achieve the prophylactic benefit. For therapeutic benefit means the eradication or improvement of the fundamental disorder to be treated and / or the eradication or improvement of one or more of the symptoms associated with the fundamental disorder, in such a way that the patient reports an improvement in the sensation or condition, without endure that the patient can still be afflicted with the fundamental disorder. For example, administration of a compound to a patient suffering from an allergy provides therapeutic benefit not only when the fundamental allergic response is eradicated or improved, but also when the patient reports a decrease in the severity or duration of symptoms associated with the allergy after exposure to the allergen. As another example, the therapeutic benefit in the context of asthma includes an improvement in breathing after the onset of an asthmatic attack, or a reduction in the frequency or severity of asthmatic episodes. The therapeutic benefit also includes stopping or slowing down the progress of the disease, with respect to whether the improvement is made. For prophylactic administration, the compound can be administered to a patient at risk of developing one of the previously described diseases. For example, if it is not known if a patient is allergic to a particular drug, the compound can be administered prior to administration of the drug to avoid or improve an allergic response to the drug. Alternatively, prophylactic administration can be applied to prevent the onset of symptoms in a patient diagnosed with the fundamental disorder. For example, a compound can be administered to one suffering from allergies prior to the expected exposure to the allergen. The compounds can also be administered prophylactically to healthy individuals who were repeatedly exposed to agents known to be one of the diseases described above, to prevent the onset of the disorder. For example, a compound can be administered to a healthy individual who is repeatedly exposed to an allergen known to induce allergies, such as latex, in an effort to prevent the individual from developing an allergy. Alternatively, a compound can be administered to a patient suffering from asthma, prior to participation in activities which activate asthma attacks to decrease the severity of, or to avoid altogether, an asthmatic episode. The amount of compound administered will depend on a variety of factors, including, for example, the particular indication to be treated, the mode of administration, whether the desired benefit is prophylactic or therapeutic, the severity of the indication to be treated and the age and patient weight, the bioavailability of the particular active compound, etc. The determination of an effective dosage is also within the capabilities of those skilled in the art.

Effective dosages can be estimated initially from in vitro assays. For example, an initial dosage for use in animals, can be formulated to achieve a circulating serum or blood concentration of an active compound that is at or above an IC50 of the particular compound, as measured in an in vitro assay, such such as CHMC or BMMC in vitro and other in vitro assays described in the Examples section. The dosage calculation to achieve such circulating serum or blood concentrations taking into account the bioavailability of the particular compound is also within the capabilities of those skilled in the art. For guidance, the reader is referred to Fingí &IsE ; Woodbury, "General Principies," Jn: Goodman and Gilman's The Pharmaceutical Basis of Therapeutics, Chapter 1, pp. 1-46, last edition, Pagamonon Press, and references cited in this document. Initial dosages can also be estimated from in vivo data, such as animal models. Animal models useful for testing the efficacy of compounds for treating or preventing the various dses described above are well known in the art. Appropriate models of allergic reactions or hypersensitivity are described in Foster, 1995, Allergy 50 (21Suppl): 6-9, discussion 34-38 and Turnas et al. , 2001, J. Allergy Clin. Immunol. 107 (6): 1025-1033. Suitable animal models of allergic rhinitis are described in Szelenyi et al. , 2000, Arzneimittelforschung 50 (11): 1037-42; Kawaguchi et al. , 1994, Clin. Exp. Allergy 24 (3): 238-244 and Sugi oto et al. , 2000, Immunopharmacology 48 (1): l-7. The appropriate animal models of allergic conjunctivitis are described in Carreras et al. , 1993, Br. J. Ophthalmol. 77 (8): 509-514; Saiga et al. , 1992, Ophthalmic Res. 24 (l): 45-50; and Kunert et al. , 2001, Invest. Ophthalmol. Vis. Sci. 42 (11): 2483-2489. Suitable animal models of systemic mastocytosis are described in O'Keefe et al. , 1987, J. Vet. Intern. Med. 1 (2): 75-80 and Bean-Knudsen et al. , 1989, Vet. Pathol. 26 (l): 90-92. The appropriate animal models of hyper IgE syndrome are described in Claman et al. , 1990, Clin. Immunol. Immunopathol. 56 (1): 46-53. Suitable animal models of B-cell lymphoma are described in Hough et al. , 1998, Proc. Nati Acad. Sci. USA 95: 13853-13858 and Hakim et al. , 1996, J. Immunol. 157 (12): 5503-5511. Suitable animal models of atopic dses, such as atopic dermatitis, atopic eczema and atopic asthma, are described in Chan et al. , 2001, J. Invest. Dermatol. 117 (4): 977-983 and Suto et al. , 1999, Int. Arch. Allergy Immunol. 120 (Suppl 1): 70-75. Those skilled in the art can routinely adapt such information to determine dosages suitable for administration to humans. Additional suitable animal models are described in the Examples section.

The dosage amounts will typically be in the range of about 0.0001 or 0.001 or 0.01 mg / kg / day, up to about 100 mg / kg / day, but may be higher or lower, depending on, among other factors, the activity of the compound, its bioavailability, the mode of administration and several factors discussed above. The amount and range of dosage can be adjusted individually to provide plasma levels of the compound (s) which are sufficient to maintain the therapeutic or prophylactic effect. For example, the compounds can be administered once a week, several times a week (for example, every third day), once a day or multiple times per day, depending on, among other things, the mode of administration, the indication specific to be treated and the judgment of the prescribing specialist. In cases of local administration or selective absorption, such as local topical administration, the effective local concentration of the active compound (s) can not be related to the concentration of the plasma. Experts in the art will be able to optimize effective local dosages without undue experimentation. Preferably, the compound (s) will provide therapeutic or prophylactic benefit, without causing substantial toxicity. The toxicity of the compound (s) can be determined using standard pharmaceutical procedures. The dose ratio between the toxic and therapeutic (or prophylactic) effect is the therapeutic index. Compounds (s) that exhibit high therapeutic indices are preferred. Having described the invention, the following examples are offered by way of illustration and not limitation.

EXAMPLES Compounds 2,4-pyrimidinediamine A variety of N 4-substituted-N 2 -monosubstituted 4-pyrimidinediamines were prepared, based on methods described herein. Such compounds are represented in Table 1. 2-, 4-pyrimidinediamine compounds of the invention, inhibit the degranulation mediated by the FceRI receptor The ability of the 2,4-pyrimidinediamine compounds of the invention, to inhibit IgE-induced degranulation, was demonstrated in a variety of cell-based cell assays cultured human mast (CHMC) and / or cells derived from mouse bone marrow (BMMC). Inhibition of degranulation was measured at both low and high cell density to quantify the release of the granule-specific tryptase, histamine and hexosaminidase factors.

Inhibition of release and / or synthesis of lipid mediators was assessed by measuring the release of leukotriene LTC4 and inhibition of release and / or cytokine synthesis was monitored by quantifying TNF-α, IL-6 and IL-13. Tryptase and hexosaminidase were quantified using fluorogenic substrates as described in their respective examples.

Histamine, TNF-α, IL-6, IL-13 and LTC4 were quantified using the following commercial ELISA kits: histamine (Immunotech # 2015, Beckman Coulter), TNFa (Biosource # KHC3011), IL-6 (Biosource # KMC0061), IL-13 (Biosource # KHC0132) and LTC4 (Cayman Chemical # 520211). The protocols of the various tests are provided below.

Culture of Human Mast Cells and Basophils Human mast cells and basophils were cultured from CD34-negative progenitor cells, as described below (see also, the methods described in the co-pending US application Serial No. 10 / 053,355, filed on November 8, 2001, description of which is incorporated herein by reference).

Preparation of Complete Medium STEMPRO-34 To prepare the complete medium STEMPRO-34 ("CM"), 250 mL of serum free medium STEMPRO-34 ™ ("SFM", GibcoBRL, Catalog No. 10640) was added to a flask of filter.

To this was added 13 mL of Nutrient Supplement STEMPRO-34 ("NS", GibcoBRL, Catalog No. 10641) (prepared as described in more detail below). The NS container was rinsed with approximately 10 mL of SFM and the rinse was added to the filter flask. After the addition of 5 mL of L-glutamine (200 mM; Mediatech, Catalog No. MT 25-005-CI and 5 mL 100X penicillin / streptomycin ("pen-strep", HyClone, Catalog No. SV30010), the volume was brought to 500 mL with SFM and the solution was filtered. The most variable aspect to prepare the MC is the method by which the NS is frozen and mixed prior to the addition to the SFM. The NS should be frozen in a water bath at 37 ° C and stirred, not in vortices or shaken, until it is completely in solution. While stirring, it is noted if there are some lipids that are not yet in solution. If the lipids are present and the NS is not uniform in appearance, it is returned to the water bath and the process of stirring until it is uniform in appearance is repeated. Sometimes this component comes into solution immediately, sometimes after a couple of cycles of stirring and sometimes not. If after a couple of hours the NS is still not in solution, a fresh unit is discarded and frozen. The NS that does not appear uniform after freezing should not be used.

Expansion of CD34 + cells A relatively small number of CD34-positive (CD34 +) cell-initiating population (1-5 x 106 cells) expanded to a relatively large number of CD34-negative progenitor cells (approximately 2-4 x 106 cells) , using the culture medium and methods described below. CD34 + cells (from a single donor) were obtained from Allcells (Berkeley, CA). Because there is a degree of variation in the quality and number of CD34 + cells that the Allcells typically provide, newly delivered cells were transferred to a 15 mL conical tube and brought up to 10 L in CM prior to use. At day 0, a cell count was performed on the viable cells (bright phase), and the cells were centrifuged at 1200 rpm to form pellets. The cells were resuspended at a density of 275,000 cells / mL with CM containing 200 ng / mL of recombinant human stem cell factor ("SCF", Peprotech, Catalog No. 300-07) and 20 ng / mL of ligand flt- 3 human (Peprotech, Catalog No. 300-19) ("medium CM / SCF / flt-3"). At about day 4 or 5, the culture density was verified by performing a cell count and the culture was diluted to a density of 275,000 cells / mL with fresh CM / SCF / flt-3 medium. Approximately on day 7, the culture was transferred to a sterile tube and a cell count was performed. The cells were centrifuged at 1200 rpm and resuspended at a density of 275,000 cells / mL with fresh CM / SCF / flt-3 medium. The cycle was repeated, starting from day 0, a total of 3-5 times over the expansion period. When the culture is large and is maintained in multiple flasks and is resuspended, the contents of all the flasks are combined in a single container prior to performing a cell count. This ensures that an accurate cell count is achieved, and provides a degree of uniformity of treatment for the entire population. Each flask is verified separately to determine contamination under the microscope, prior to the combination, to prevent contamination of the entire population. Between days 17-24, the crop begins to decline (that is, approximately 5-10% of the total number of cells dies), and fails to expand as rapidly as before. The cells are then monitored on a daily basis during this time, as a complete failure of the culture can take place in as little as 24 hours. Once the decline has begun, the cells are counted, centrifuged descending at 850 rpm for 15 minutes, and resuspended at a density of 350,000 cells / mL in CM / SCF / flt-3 medium to induce one or more divisions outside the culture. . The cells are monitored daily to avoid culture failure. When more than 15% of cell death is evident in parental cell cultures and some wastes are present in the culture, the CD34-negative progenitor cells are ready to be differentiated.

Differentiation of CD34-Negative Progenitor Cells in Mucosal Mast Cells. A second phase was performed to convert the expanded CD34-negative progenitor cells into differentiated mucosal mast cells. These cultured human mucosal mast cells ("CHMC") are derived from CD34 + cells isolated from umbilical cord blood and treated to form a proliferated population of CD34-negative progenitor cells, as described above. To produce the CD34-negative progenitor cells, the resuspension cycle for the culture was the same as that described above, except that the culture was seeded at a density of 425,000 cells / mL and 15% additional medium was added at about the day fourth or fifth without performing a cell count. Also, the cytokine composition of the medium was modified, such that it contains SCF (200 ng / mL) and recombinant human IL-6 (200 ng / mL; Prepotech, Catalog No. 200-06 reconstituted at 100 ug / mL; in sterile 10 mM acetic acid) ("CM / SCF / IL-6 medium").

The phases I and II together, last approximately 5 weeks. Some disposal and debris in the crop is evident for 1-3 weeks and there is a period for 2-5 weeks, during which, a small percentage of the crop is not larger in suspension, but instead, it is attached to the surface of the culture vessel. As during Phase I, when the culture is resuspended on day seven of each cycle, the contents of all the flasks are combined in a single container prior to performing a cell count to ensure uniformity of the entire population. Each flask is verified separately to determine contamination under the microscope prior to the combination to prevent contamination of the entire population. When the flasks are combined, approximately 75% of the volume is transferred to the communal container, leaving in addition, approximately 10 mL or so in the flask. The flask containing the remaining volume was beaten abruptly and laterally to dislodge the bound cells. The pounding was repeated at a right angle on the first hit to completely dislodge the cells. The flask was tilted at a 45 degree angle for a couple of minutes before the remaining volume was transferred to the counting vessel. The cells were centrifuged at 950 rpm for 15 minutes, before planting 35-50 mL per flask (at a density of 425,000 cells / mL).

Differentiation of CD34-Negative Progenitor Cells in Connective Tissue-like Mast Cells A proliferated population of CD34-negative progenitor cells was prepared as above, and treated to form a positive tryptase / chymase (connective tissue) phenotype. The methods are performed as described above for the mucosal mast cells, but with the replacement of IL-4 by IL-6 in the culture medium. The cells obtained are typical of connective tissue mast cells.

Progenitor Cell Differentiation of CD34-Negative Progenitor Cells in Basophil Cells A proliferated population of CD34-negative progenitor cells was prepared as described in Section 7.2.1.3, above, and was used to form a proliferated population of basophil cells. The CD34-negative cells are treated as described for the mucosal mast cells, but with the substitution of IL-3 (at 20-50 ng / mL) for IL-6 in the culture medium.

Activation of Low Cellular Density IgE CHMC: Triptase and LTC4 assays To duplicate plates with 96 U-bottom cavities (Costar 3799), 65 ul of compound dilutions or control samples were added, which have been prepared in MT [137 mM NaCl, 2.7 mM KCl, 1.8 mM CaCl2, 1.0 mM MgCl2, 5.6 mM Glucose, 20 mM Hepes (pH 7.4), 0.1% Bovine Serum Albumin (Sigma A4503)] containing 2% MeOH and 1% DMSO. CHMC cells pelletized (980 rpm, 10 min) and resuspended in pre-warmed MT. 65 ul of cells were added to each 96-well plate. Depending on the degranulation activity for each particular CHMC donor, 1000-1500 cells / well are loaded. They are mixed four times in succession by an incubation of 1 hour at 37 ° C. During 1 hour of incubation, 6X anti-IgE solution [rabbit anti-human IgE (1 mg / ml, Bethyl Laboratories A80-109A) diluted 1: 167 in MT buffer] is prepared. Cells are stimulated by adding 25 ul of 6X anti-IgE solution to the appropriate plates. 25 ul of MT are added to unstimulated control cavities. It is mixed twice after the addition of anti-IgE. Incubate at 37 ° C for 30 minutes. During the 30 minute incubation, 20 mM of base tryptase substrate solution [(Z-Ala-Lys-Arg-AMC 2TFA; Enzyme Systems Products # AMC-246)] 1: 2000 is diluted in tryptase assay buffer [0.1 M Hepes (pH 7.5), 10% w / v Glycerol, 10 uM Heparin (Sigma H-4898) 0.01% NaN3]. The plates are centrifuged at 1000 rpm for 10 minutes to form cell pellets. They are transferred 25 ul of supernatant is added to a 96-well dark-bottom plate and 100 ul of freshly diluted tryptase substrate solution is added to each well. Plates are incubated at room temperature for 30 minutes. The optical density of the plates is read at 355 nm / 460-nm in a spectrophotometric plate reader. Leukotriene C4 (LTC4) is also quantified using an ELISA kit in appropriately diluted supernatants (determined empirically for each donor cell population, so that the measurements of the samples fall within the standard curve), following the supplier's instructions.

High Cellular Density IgE Activation: Degranulation Assays (Triptase, Histamine), Leukotriene (LTC) and Cytokine (TNAlfa, IL-13) Cultured human mast cells were sensitized (CHMC) for 5 days with IL-4 (20 ng / ml), SCF (200 ng / ml), IL-6 (299 ng / ml) and Human IgE (CP 1035K of Cortx Biochem, 100-500 ng / ml, depending on generation) in CM medium. After sensitization, cells are counted, pelletized (1000 rpm, 5-10 minutes), and resuspended at 1-2 x 106 cells / ml in TM buffer. 100 ul of cell suspension is added to each well and 100 ul of dilutions of the compound. The concentration of the final vehicle is 0.5% DMSO. They are incubated at 37 ° C (5% C02) for 1 hour. After 1 hour of compound treatment, the cells are stimulated with anti-6E IgE. The cavities are mixed with the cells and the plates are left to incubate at 37 ° C (5% C02) for one hour. After 1 hour of incubation, cell pellets are formed (10 minutes, 1000 RPM) and 200 ul are collected per cavity of the supernatant, being careful not to disturb the pellet. The supernatant plate is placed on ice. During the 7 hour stage (see below), the tryptase assay is performed in the supernatant which has been diluted 1: 500. The cell pellet is resuspended in 240 ul of CM medium containing 0.5% DMSO and corresponding to the concentration of the compound. CHMC cells are incubated for 7 hours at 37 ° C (C02 at 5%). After incubation, cell pellets are formed (1000 RPM, 10 minutes) and 225 ul are collected per well and placed at -80 ° C until they are ready to perform the ELISA. ELISAs are performed on appropriately diluted samples (determined empirically by each cell population donor, so that the sample measurements fall within the standard curve), following the supplier's instructions.

Results The results of the low density CHMC assays are given in Table 1. In Table 1, all reported values are IC50 (in μM). Most of the compounds tested have an IC0 of less than 10 μM, with many having IC 50 in the sub-micromolar range. In Table 1, all reported values are IC50 (in μM). A value of "-" indicates an IC50 > 10 μM, without measurable activity at a concentration of 10 μM. Most of the compounds tested have an IC 50 of less than 10 μM, with many having IC 50 in the sub-micromolar range. A value of "+" indicates an IC50 < 10 μM. Of the compounds tested, the BMMC values are comparable to those noted by the CHMC results.

The 2,4-pyrimidinediamine compounds of the invention selectively inhibit the upstream IgE receptor cascade to confirm that many of the 2,4-pyrimidinediamine compounds of the invention exert their inhibitory activity by blocking or inhibiting the signal transduction cascade of the receptor. Early IgE, several of the compounds were tested in cell assays to determine degranulation induced by ionomycin, as described below.

Ionomycin Activation of Low Cellular Density CHMC: Tryptase Assay The assays for the degranulation of mast cells induced by ionomycin were carried out as described by the low density IgE activation assays CHMC (Section 7.2.2, supra), with the exception that during the 1-hour incubation, the 6X ionomycin solution [5 mM ionomycin (Sigma 1-0634) in MeOH (base solution), diluted 1: 416.7 in TM buffer (2 μM final)], was prepared and the cells were stimulated by adding 25 μl of the 6X ionomycin solution to the appropriate plates.

Results The results of the ionomycin induced degranulation assays, reported as IC50 values (in μM), are given in Table 1. Of the tested active compounds (ie, those that inhibit IgE-induced degranulation), the vast majority does not inhibit ionomycin-induced degranulation, confirming that these active compounds selectively inhibit the signal transduction cascade of the early (or upstream) IgE receptor. In Table 1, all reported values are IC50 (in μM). A value of "-" indicates an IC50 > 10 μM, without measurable activity at a concentration of 10 μM. A value of "+" indicates an IC50 < 10 μM.

Compounds 2,4-pyrimidinediamine inhibit Syk kinase in biochemical assays Many of the 2,4-pyrimidinediamine compounds were tested for the ability to inhibit phosphorylation catalyzed by Syk kinase from a peptide substrate in a biochemical fluorescence polarization assay with Syk kinase isolated. In this experiment, the compounds were diluted in 1% DMSO in kinase buffer (20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg / mL Bovine Range Globulin acetylated). The compound was mixed in 1% DMSO (0.2% final DMSO), with ATP / substrate solution at room temperature. The Syk kinase (Upstate, Lake Placid NY) was added to a final reaction volume of 20 uL, and the reaction was incubated for 30 minutes at room temperature. The final reaction conditions of the enzyme were 20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg / mL Acetylated Bovine Range Globulin, 0.125 ng Syk, 4 uM of ATP, 2.5 uM peptide substrate (biotin- EQEDEPEGDYEEVLE-CONH2, SynPep Corporation). EDTA (10 mM final) / anti-phosphotyrosine antibody (final IX) / fluorescent phosphopeptide indicator (0.5X final) was added in an FP dilution buffer to stop the reaction to a total volume of 40 uL in accordance with the manufacturer's instructions (Pan Vera Corporation). The plate was incubated for 30 minutes in the dark at room temperature. Plates were read on a Polarion fluorescence polarization plate reader (Tecan). The data were converted to amounts of phosphopeptide present using a calibration curve generated by competition with the phosphopeptide competitor provided in the Tyrosine Kinase Assay Kit, Green (Pan Vera Corporation). These data, shown in Table 1, demonstrate that the majority of all tested compounds inhibit phosphorylation of Syk kinase with IC50 in the submicromolar range. A vast majority of the compounds tested inhibit phosphorylation of Syk kinase with IC50 in the micromolar range. In Table 1, all reported values are in IC50 (in μM). A value of "-" indicates an IC50 > 10 μM, without measurable activity at a concentration of 10 μM. A value of "+" indicates an IC50 < 10 μM.

No. Name of Compound Physical Data Triptase Triptase Triptase fp_sik Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt I E, 8pt Ion, 3pt? NMR (DMSO-d6): d 8.08 (S) -5-Fluoro-N2- (d, 1H), 7.95 (s, 1H), 7.58 (d, (indazol-6-yl) -N4- (2-1H ), 7.40 (m, 1H), 7.25 (m, 200 methyl-3-oxo-2H, 4H-3H), 6.94 (m, 1H), 4.80 (m, + benz [1,4] oxazin-6-yl ) - 1H), 1.40 (s, 3H); LCMS: 2,4-pMmidindiamine purity: 96%; MS (m / e): 406 (MH +). 'H NMR (DMSO-d6): d 8.17 (d, 1H), 8.08 (s, 1H), 7.80 (s, (S) -5-Fluoro-N2- (l-1H), 7.52 (m, 1H) , 7.32 (, methyladazol-6-yl) -N4- 1H), 7.17 (m, 2H), 6.94 (m, 201 (2-methyl-3-oxo-2H, 4H-1H), 4.60 (m, 1H) 3.77 (s, benz [1,4] oxazin-6-yl) -3H), 1.45 (s, 3H); LCMS: 2,4-pyrimidinediamine purity: 94%; MS (m / e): 420 (MH +). 'H NMR (DMSO-d6): d 8.01 (S) -N2- (3.5- (d, 1H), 7.28 (m, 2H), 7.20 Dimethylphenyl) -5-fluoro- (s, 2H), 6.95 (m, 1H), 6.58 N4- (2-methyl-3-oxo-202 (s, 1H), 4.63 (m, 1H), 3.77 2H, 4H-benz [1,4] oxazin- (s, 3H) , 2.07 (s, 6H), 1.42 (d, 6-yl) -2,4-pyripidinediamine 3H); LCMS: purity: 92%; MS (m / e): 393 (MH +). ? NMR (DMSO-d6): d 8.02 N4- (3,4-Dihydro-3,3- (d, 1H), 6.98 (m, 2H), 6.90 dimethyl-2H, 4H- (m, 2H), 6.80 ( m, 1H), 6.03 benz [1,4] oxazin-6-yl) -203 (s, 1H), 3.72 (s, 2H), 3.60 (s, + N2- (3,5-dimethoxyphenyl) - + 6H ), 1.05 (s, 6H); LCMS: 5-fluoro-2,4-purity: 96%; MS (m / e): 425 pyrimidinediamine (MH +). JH NMR (DMSO-d6): d 8.01 (R) -N2- (3.5- (d, 1H), 7.28 (m, 2H), 7.20 Dimethylphenyl) -5-fluoro- (s, 2H), 6.95 ( m, 1H), 6.58 N4- (2-methyl-3-oxo-04 (s, 1H), 4.63 (m, 1H), 3.77 + 2H, 4H-benz [1,4] oxazin- (s, 3H) , 2.07 (s, 6H), 1.42 (d, 6-ñ) -2.4- 3H); LCMS: purity: 92%; pyrimidinthamine MS (m / e): 393 (MH +). Q) -5-Fluoro-N2- [6- (2- 'H NMR (MeOD-d4): d 7.75 hydroxyethyl) -2.3- (d, 1H), 7.38 (, 1H), 7.02 diMdropirrol [l, 2.3- (m, 3H), 6.78 (m, 2H), 4.54 d, e] benzoxazin-8-yl] - (, 1H), 4.4 (m, 2H), 4.14 05 N4- (2-methyl- 3-oxo- (m, 2H), 3.62 (m, 2H), 3.62 2H, 4H-benz [1, 4] oxazin- (m, 2H), 2.80 (m, 2H), 1.41 6-ü) -2 , 4- (d, 3H); LCMS: purity: 93%; pyrimidinediamine MS (m e): 491 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3? T IgE, 8pt Ion, 3pt N4- (3,4-DiHdro-3,3- ? NMR (MeOD-d4): d 7.62 dimethyl-2H, 4H- (d, 1H), 7.04 (s, 1H), 6.98 benz [1,4] oxazin-6-yl) -5- (m, 2H) , 6.75 (m, 1H), 6.59 fluoro-N2- [6- (2- (m, TH), 4.47 (m, 1H), 4.4 206 hydroxyethyl) -2.3- (, 2H), 4.14 (m, 2H), 3.62 dihydropyrrolfl, 2.3- (m, 4H), 2.80 (m, 2H), 1.07 d, e] benzoxazin-8-yl] - (s, 6H); LCMS: purity: 2,4-? Irimidiadiamine 98%; MS (m / e): 491 (MH +). Salt of the acid! H NMR (MeOD-d4): d 7.98 benzenesulfonic of (R) - (d, 1H), 7.82 (m, 2H), 7.48 N2- (3-Chloro-4- (s, 1H), 7.41 (m, 3H), 7.25 methoxyphenyl) -5-fluoro- (dd, 1H), 7.15 (m, 3H), 6.94 207 + N4- (2-methyl-3-oxo- (d, 1H), 4.62 (q , 1H), 3.82 2H, 4H-benz [1,4] oxazin- (s, 3H), 1.50 (d, 3H), CLEM: 6-yl) -2.4- purity: 97%; MS (m / e): 430 pyrimidiamine (MH +). Salt of JH NMR acid (MeOD-d4): d 7.98 methanesulfonic acid of (R) - (d, 1H), 7.48 (s, 1H), 7.25 N2- (3-Chloro-4- (dd, 1H), 7.15 ( m, 3H), 6.94 methoxyphenyl) -5-fluoro-208 (d, 1H), 4.62 (q, 1H), 3.82 N4- (2-methyl-3-oxo- + (s, 3H), 2.68 (s, 3H), 1.50 (d, 2H, 4H-benz [1,4] oxazin-3H); LCMS: purity: 98%; 6-yl) -2.4-MS (m / e): 430 (MH +). pyridinamine JH NMR (DMSO-d6): d 8.19 Salt of the acid (1S) - (d, 1H), 7.62 (, 1H), 7.38 camphorsulfonic of (R) - (m, 1H), 7.21 (m, 1H) , 7.12 N2- (3-Chloro-4- (, 2H), 6.91 (d, 1H), 4.62 methoxife l) -5-fluoro- (q, 1H), 3.82 (s, 3H), 3.40 209 N4- ( 2-methyl-3-oxo- (q, 1H), 2.91 (m, 1H), 2.61 + 2H, 4H-benz [1,4] oxazin- (m, 1H), 2.38 (, 1H), 2.22 6- il) -2.4- (m, 1H), 1.85 (m, 2H), 1.40 pyrimidindiamioa (d, 3H), 1.31 (m, 2H), 1.03 (s, 'H NMR (DMSO-d6): d 8.16 (d, 1H), 8.08 (s, 1H), 7.80 (s, (R) -5-Fluoro-N2- (l-1H), 7.52 (m, 1H), 7.32 (m, methydazol-6-yl) -N4- 1H), 7.17 (m, 2H), 6.94 (m, 210 (2-methyl-3-oxo-2H, 4H-1H), 4.60 (m, 1H), 3.77 (s, benz [l, 4 ] oxazin-6-yl) -3H), 1.45 (s, 3H); LCMS: 2,4-puyndiphenimine purity: 97%; MS (m / e): 420 (MH +). JH NMR chloride salt (DMSO -d6): d 8.12 hydrogen of (R) -N2- (3- (d, 1H), 7.41 (dd, 1H), 7.22 Chloro-4-methoxyphenyl) -5- (m, 3H), 6.97 (m, 1H), 4.61 211 fluoro-N4- (2-methyl-3 - + + (q, 1H), 3.78 (s, 3H), 1.40 (d, oxo-2H, 4H-3H); M: purity: 97%; benz [1,4] oxazin-6-yl) -MS (m / e): 430 (MH +). 2,4-? Irimidmdiamine No. Name of Compound Physical Data Triptase Triptase Triptase S sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T: H NMR (DMSO-d6 ): d 8.19 Salt of the acid (lR) - (-) - (d, 1H), 7.62 (m, 1H), 7.38 camphorsulfonic of (R) - (m, 1H), 7.21 (m, 1H), 7.12 N2 - (3-Chloro-4- (m, 2H), 6.91 (d, 1H), 4.62 methoxyphenyl) -5-fluoro- (q, 1H), 3.82 (s, 3H), 3.40 212 N4- (2-methyl) -3-oxo- + + (q, 1H), 2.91 (m, 1H), 2.61 2H, 4H-benz [1,4] oxazin- (m, 1H), 2.38 (m, 1H), 2.22 6-il ) -2.4- (m, 1H), 1.85 (m, 2H), 1.40 pyrimidinediamine (d, 3H), 1.31 (m, 2H), 1.03 (s, l .. NMR (DMSO-d6): d 8.17 (R) -N2- (3-Chloro-4- (s, 1H), 7.98 (d, 1H), 7.43 methoxy-6-methylphenyl) -5- (m, 1H), 7.32 (m, 1H), 7.15 fluoro-N4- (2-methyl-3- (s, 1H), 6.95 (s, 1H), 6.72 (d, 213 oxo-2H, 4H-1H), 4.58 (m, 1H), 3.90 (s, benz) [1,4] oxazin-6-yl) -3H), 2.17 (s, 3H), 1.38 (d, 2,4-pyrimidinediamine 3H), LCMS: purity: 97%, MS (m / e): 444 ( MH +).! H NMR (DMSO-d6): d 8.17 (S) -N2- (3-Chloro-4- (s, 1H), 7.98 (d, 1H), 7.43 methoxy-6-methylphenyl) -5- (m, 1H), 7.32 (m, 1H), 7.15 fluoro-N4- (2-methyl-3- (s, 1H), 6.95 (s, 1H) , 6.72 (d, 214 oxo-2H, 4H-1H), 4.58 (m, 1H), 3.90 (s, benz [1,4] oxazin-6-yl) -3H), 2.17 (s, 3H), 1.38 (d, 2,4-? iripúdindiamir? a 3H); LCMS: purity: 99%; MS (m / e): 444 (MH +). 1 H NMR (DMSO-d 6): d (S) - (3-Chloro-4,6- 1.38 (d, 3H), 3.82 (s, 3H), dimethoxiferu) -5-fluoro-3.90 (s, 3H), 4.58 (q, 1H), N4- (2-methyl-3-oxo-6.85 (m, 2H), 7.19 (m, 1H), 215 2H, 4H ~ benz [1,4] oxazin- 7.37 (m, 1H ), 7.43 (m, 1H), + 6-yl) -2.4-7.59 (s, 1H), 8.17 (m, 2H) pyrimidinediamine purity: 99%; MS (m / e): 460 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3-Chloro-4-methoxy-1.38 (s, 6H), 2.17 (s, 3H), 6-methylphenyl) -N 4 - (3,4- 3.64 (s, 3H), 3.81 (s, 3H), dihydro-353-dimethyl-6.48 (m, 1H), 6.77 (, 1H), 216 + 2H, 4H-benz [1,4] oxazin-6.93 (m, 1H), 6.99 (m, 1H), + 6-yl) -5-fluoro-2,4- 7.41 (s, 1H), 7.82 (d, 1H) p? ± midindiamine purity: 99%; MS (m / e): 444 (MH +). X H NMR (DMSO-d 6): d N 4 - (3,4-Dihydro-2 H, 4 H-8.19 (m, 1 H), 8.15 (d, 1 H), benz [1,4] oxazin-6-yl) -5 - 7.78 (m, 1H), 7.39 (m, 2H), 217 fluoro-N2- [3- (oxazole-2- 6.90 (m, 1H), 6.47 (m, 1H), + + il) phenyl] -2 , 4- 4.07 (m, 2H), 3.22 (m, 2H); pyrimidinediamine LCMS: purity: 97%; MS (m / e): 405 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase? sik Com LD, LD, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N4- (3,4-Dihydro-3,3- 1.18 (s, 6H), 3.81 (s, 2H), dimethyl-2H, 4H-6.77 (m, 1H), 6.93 (m, benz [1,4] oxazin-6-yl) -5- 1H), 6.99 (m, 1H) ), 7.38 (m, 218 + + fluoro-N2- [3- (oxazole-2H), 7.63 (m, 1H), 7.71 (m, il) phenyl] -2.4- 1H), 8.12 (s) , 1H), 8.22 (m, pmmidindia ina 2H) purity: 99%; MS (m / e): 433 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (oxazole-4.50 (s, 2H), 6.78 (m, 1H), 2-yl) phenyl] -N 4 - (3-oxo- 7.18 (m, 1H), 7.23 (m, 1H), 219 2H, 4H-benz [1,4] oxazin- 7.38 (, 2H), 7.59 (m, 1H), + + 6-yl) -2.4- 7.77 (m, 1H), 8.22 (m, 3H) pyrimidinediamine purity: 99%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (oxazole-4.50 (s, 2H), 6.78 (m, 1H), 2-yl) phenyl] -N 4 - (3-oxo- 7.18 (m, 1H), 7.23 (m, 1H), 220 2H, 4H-benz [1,4] oxazin- 7.41 (m, 2H), 7.59 (m, 1H), + + 7-yl) -2.4 - 7.78 (m, 1H), 8.22 (, 3H) pyrimidinediamine purity: 97%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 - [2- (2- 1.98 (m, 1 H), 3.58 (m, 2 H), hydroxyethyl) -3-oxo-6.78 (m, 1 H), 7.18 (m, 2H, 4H-benz [1,4] oxazin-221 1H), 7.38 (m, 3H), 7.57 + 6-yl] -N2- [3- (oxazole-2- (m, 1H), 7.79 (m, 1H), 8.22 il) phenyl] -2,4- (m, 2H) purity: 99%; Pyrimidinediamine EM (m / e): 463 (MH +). : H NMR (DMSO-d6): d 8.29 (m, 1H), 8.17 (d, 1H), N4- (3,4-Dihydro-2H, 4H- 7.76 (, 1H), 7.59 (m, 3H), Benz [1,4] oxazin-6-yl) -5- 6.90 (m, 1H), 6.77 (m, 1H), 222 fluoro-N2- [4- (oxazole-5- + 6.62 (m, 1H) , 4.07 (m, 2H), il) phenyl] -2.4- 3.22 (m, 2H); LCMS: pyrimidinediamine purity: 90%; MS (m / e): 405 (MH +) - 1 H NMR (DMSO-d 6): d N 4 - (3,4-Dihydro-3,3-1.18 (s, 6H), 3.80 (s, 2H), dimethyl- 2H, 4H- 6.71 (m, 2H), 6.95 (m, benz [1,4] oxazin-6-yl) -5-223 H, 7.51 (s, 1 H), 7.69 (m, + + fluoro-N2 - [4- (oxazole-5H), 7.69 (m, 2H), 8.20 (d, yl) phenyl] -2.4- 1H), 8.38 (s, 1H) purity: 95 pyrimia diamine%; MS (m / e): 433 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 5-Fluoro-N2- [4- (oxazole-4.68 (s, 2H), 6.98 (m, 2H), 5-yl) phenyl] -N4- (3-oxo- 7.22 (m, 1H), 7.51 (s, 1H), 224 2H , 4H-benz [1,4] oxazin- 7.57 (m, 2H), 7.78 (m, 2H), + + 6-yl) -2.4- 8.28 (d, 1H), 8.38 (s, 1H) pyridine idindiamine purity: 98%; MS (m / e): 419 (MH +). ll? NMR (DMSO-d6): d 8.28 (S) -5-Fluoro-N4- (2- (s, 1H), 8.22 (d, 1H), 7.62 methyl-3-oxo-2H, 4H- (m, 2H ), 7.57 (m, 2H), 7.49 benz [1,4] oxazin-6-yl) - 225 (s, 1H), 7.25 (m, 2H), 6.98 + N2- [4- (oxazol-5-yl) - (m, 1H), 4.62 (q, 1H), 1.42 fenü] -2,4- (d, 3H), CLEM: purity: pyrimidindiamine 88%, MS (m / e): 433 (MH +). 1H NMR (DMSO-d6): d 5-Fluoro-N2- [4- (oxazole-4.66 (s, 2H), 6.98 (m, 2H), 5-yl) feml] -N4- (3-oxo- 7.22 (m , 1H), 7.51 (s, 1H), 226 2H, 4H-benz [1,4] oxazin- 7.57 (, 2H), 7.76 (m, 2H), + 7-il) -2.4- 8.28 (d , 1 H), 8.38 (s, 1 H) pyrimidinediamine purity: 92%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 - [2- (2- 1.93 (m, 2H), 3.58 (, 2H), hydroxyethyl) -3-oxo- 4.62 (m, 1H), 6.98 (m, 2H), 2H, 4H-benz [1,4] oxazin- 7.22 (m, 2H) ), 7.51 (s, 1H), 227 6-yl] -N2- [4- (oxazole-5-7.57 (m, 2H), 7.76 (m, 2H), + il) phenyl] -2.4- 8.28 (d, 1H), 8.38 (s, 1H) pyrimidmdiamine purity: 95%; MS (m / e): 463 (MH +). 'H NMR (DMSO-d6): d 8.29 N4- (3,4-Dihydro- 4- (s, 1H), 8.15 (d, 1H), 7.76 methyl-2H- (m, 1H), 7.57 (m, 3H), 6.88 benz [1,4] oxazin-6-yl) -5- (m, 1H), 6.77 (m, 1H), 6.62 228 + fluoro-N2- [4- ( oxazole-5- (m, 1H), 4.10 (m, 2H), 3.20 ü) phenyl] -2.4- (m, 2H), 2.80 (s, 3H); pyripidinediamine LCMS: purity: 94%; MS (m / e): 419 (MH +). JH NMR (DMSO-d6): d N4- (3,4-Dihydro-4- 8.37 (s, 1H), 8.19 (d, 1H), methyl-2H- 7.61 (m, 5H), 7.07 (m, 2H ), benz [1,4] oxazia-7-yl) -5- 29 6.68 (, 1H), 4.22 (m, 2H), fluoro-N2- [4- (oxazole-5- + 3.22 (m, 2H) 2.81 (s, 3H); il) phenyl] -2,4-LCMS: purity: 94%; Pyrimidinediamine MS (m / e): 419 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d 8.36 5-Fluoro-N4 - (4-methyl-3 - (s, 1H), 8.20 (m, 1H), 8.19 (d, oxo-2H-1H), 7.77 (, 2H), 7.54 (m, benz [1,4] oxazin- 7-ü) - 2H), 7.37 (s, 1H), 7.25 (m, 230 N2- [4- (oxazole-5-1H), 6.97 (m, 1H), 4.58 (s, u) phenyl] -2 , 4- 2H), 2.97 (s, 3H); LCMS: pyrirmidmdiamine purity: 98%; MS (m / e): 433 (MH +). * H NMR (DMSO-d6): d 5-Fluoro-N4- (4-methyl-3- 8.34 (s, 1H), 8.20 (m, 1H), oxo-2H-8.17 (d, 1H), 7.71 ( m, 2H), benz [1,4] oxazin-6-yl) -7.54 (m, 2H), 7.33 (s, 1H), 231 N2- [4- (oxazole-5-7.5 (m, 1H), 6.92 (m, 1H), il) phenyl] -2.4-4.60 (s, 2H), 2.90 (s, 3H); pyrimidinediamine LCMS: purity: 95%; MS (m / e): 433 (MH +). : H NMR (DMSO-d6): d 8.39 N4- (3,4-Dihydro-2H, 4H- (m, 1H), 8.22 (d, 1H), 7.86 benz [1,4] oxazin-6-yl) -5- (, 1H), 7.59 (m, 4H), 6.87 232 fluoro-N2- [3- (oxazole-5- (m, 2H), 6.52 (m, 1H), 4.09 + ü) phenyl] -2 , 4- (m, 2H), 3.23 (m, 2H); pyrmidinediamine LCMS: purity: 90%; MS (m / e): 405 (MH +). 'H NMR (DMSO-d6): d 8.37 N4- (3,4-Di-dro-3,3- (s, 1H), 8.19 (d, 1H), 7.82 dimethyl-2H, 4H ~ (m, 1H) 7.63 (m, 2H), 7.50 benz [l, 4] oxazin-6-yl) -5- (s, 1H), 7.38 (m, 1H), 6.87 233 + + fluoro-N2- [3- (oxazole -5- (m, 1H), 6.65 (m, 2H), 3.82 il) phenyl] -2,4- (s, 2H), 1.19 (s, 6H); LCMS: pyriridinediamine purity: 95%; MS (m / e): 433 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (oxazole-4.42 (s, 2H), 6.61 (m, 2H), 5-yl) phenyl] -N 4 - (3-oxo- 6.95 (m, 1H), 7.51 (s, 1H), 234 2H, 4H-benz [1, 4] oxazia- 7.49 (m, 2H), 7.59 (m, 2H), + 7-ü) -2.4- 8.20 (d, 1H), 8.38 (s, 1H) pyrimidinediamine purity: 90%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 - [2- (2- 1.93 (m, 2 H), 3.58 (m, 2 H), hydroxyethyl) -3-oxo-4.62 (m, 1 H), 6.61 (m, 2H, 4H-benz [1,4] oxazin-2H), 6.95 (m, 1H), 7.51 (s, 235 + 6-yl] -N2- [3- (oxazole-5-1H), 7.49 (m, 2H), 7.59 (m, + ü) phenyl] -2,4-2H), 8.20 (d, 1H), 8.38 (s, pyrimidinediamine 1H) purity: 90%; MS (m / e): 463 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N4- (3,4 -Dihydro-4- 1.93 (m, 2H), 3.58 (m, 2H), methyl-2H- 4.62 (m, 1H), 6.61 (m, 2H), benz [1,4] oxazin-6-yl) - 5- 6.95 (m, 1H), 7.51 (s, 1H), 236 + fluoro-N2- [3- (oxazole-5- 7.49 (m, 2H), 7.59 (m, 2H), ü) phenyl] -2 , 4- 8.20 (d, 1H), 8.38 (s, 1H) pyrimidinediamine purity: 95%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (3,4-Di dro-4- 1.93 (m, 2H), 2.82 (s, 3H), methyl-2H-3.58 (m, 2H), 4.62 (m, 1H), benz [1,4] oxazin-7-yl) -5- 6.61 (m, 2H), 6.95 (m, 237 + fluoro-N2- [3- (oxazole-5-1H), 7.51 (s, 1H), 7.49 (m, il) phenyl] -2.4-2H), 7.59 (m, 2H), 8.20 (d, pyrimidinediamine 1H), 8.38 (s, 1H) purity: 95%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (3,4-Dihydro-3,3- 1.38 (s, 6H), 3.81 (s, 2H), dimethyl-2H, 4H-6.71 (m, 2H), 6.95 (m, benz [1,4] oxazin-6-yl) -5-238 1H), 7.51 (s, 1H), 7.69 (m, + + fluoro-N2- [4- (oxazole-2H), 7.69 (m, 2H), 8.20 (d, il) feml] -2.4- 1H), 8.38 (s, 1H) purity: 99 pyrimidinediamine%; MS (m / e): 433 (MH +). X H NMR (DMSO-d 6): d 8.15 5-Fluoro-N 2 - [4- (oxazole - (d 1 H), 8.10 (s, 1 H), 7.78 (m, 2-yl) phenyl] -N 4 - (3- oxo-3H), 7.14 (m, 3H), 6.97 (m, 239 2H, 4H-benz [1,4] oxazin- + 2H), 4.56 (s, 2H), LCMS: 6-yl) -2.4 - purity: 98%; MS (m / e): 419 pyrmidinediamine (MH +). ? NMR (DMSO-d6): d 8.25 (S) -5-Fluoro-N4- (2- (m, 1H), 8.22 (d, 1H), 8.12 methyl-3-oxo-2H, 4H- (m, 1H ), 7.77 (m, 2H), 7.34 benzfl, 4] oxazin-6-yl) -240 (s, 1H), 7.23 (m, 2H), 6.98 + + N2- [4- (oxazole-2- (m , 2H), 4.63 (q, 1H), 1.42 il) phenyl] -2,4- (d, 3H); LCMS: purity: 95% pyridine diamine; MS (m / e): 433 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [4- (oxazole-4.45 (s, 2H), 6.71 (, 2H), 2-yl) phenyl] -N 4 - (3-oxo-6.95 ( m, 1H), 7.51 (s, 1H), 241 2H, 4H-benz [1,4] oxazin- 7.69 (m, 2H), 7.69 (m, 2H), 7-ü) -2.4- 8.20 ( d, 1 H), 8.38 (s, 1 H) p mid diamine purity: 95%; MS (m / e): 419 (MH +). 'H NMR (DMSO-d6): d 8.25 (d5-Fluoro-N4- [2- (2-1H), 8.20 (d, 1H), 8.16 (s, 1H), hydroxyethyl) -3-oxo- 7.82 (m, 3H), 7.35 (s, 1H), 7.20 2H, 4H-benz [1,4] oxazine-242 (m, 2BT), 6.95 (m, 1H), 4.62 (m, 6-yl) -N2 - [4- (oxazole-2H), 3.58 (m, 1H), 1.95 (m, il) phenyl] -2.4- 2H); LCMS: purity: 99%; Pyrimidinediamine EM (m e): 463 (MH +).

No. Name of Compound Physical Data Triptase Triptase T rate fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N4- (2, 3-Dihydro-4- 1.93 (m, 2H), 2.80 (s, 3H), methyl-2H-3.58 (m, 2H), 4.62 (m, 1H), benzfl, 4] oxazin-6-yl) -5 - 6.71 (m, 2H), 6.95 (m, 243 fluoro-N2- [4- (oxazole-2-1H), 7.51 (s, 1H), 7.69 (, + + ü) phenyl] -2.4- 2H ), 7.69 (m, 2H), 8.20 (d, pyrimidindia iria 1H), 8.38 (s, 1H) purity: 99%; MS (m / e): 419 (MH +). J H NMR (DMSO-d 6): d 8.18 5-Fluoro-N 4 - (4-metü-3- (d, 1H), 8.14 (s, lH), 7.82 (d, oxo-2H-2H), 7.56 (m , 2H), 7.40 (m, benz [1,4] oxazin-7-yl) -244 2H), 7.30 (s, 1H), 6.95 (m, N2- [4- (oxazole-2-1H), 4.62 (s, 2 H), 2.78 (s, il) phenyl] -2,4- 3 H); LCMS: purity: 99%; pyrimidinediamine MS (m / e): 433 (MH +). ? NMR (DMSO-d6): d 8.20 5-Fluoro-N4- (4-methyl-3- (d, 1H), 8.12 (s, 1H), 7.82 (d, oxo-2H-2H), 7.55 (m, 2H), 7.40 (m, benz [1,4] oxazin-6-yl) -245 2H), 7.33 (s, 1H), 6.88 (m, N2- [4- (oxazole-2H), 4.59 ( s, 2H), 2.77 (s, ü) phenyl] -2,4- 3H); LCMS: purity: 98%; pyriridinediamine MS (m / e): 433 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (oxazole-4.45 (s, 2H), 6.78 (m, 1H), 5-ü) phenyl] -N 4 - [3-oxo- 7.18 (m, 1H), 7.38 (, 246 2H, 4H-benz [1,4] oxazin-3H), 7.57 (m, 1H), 7.79 + 6-yl] -2.4- (m, 1H), 8.22 (m, 2H) pyrimidinediamine purity: 93%; MS (m / e): 419 (MH +). 1 H NMR (DMSO-d 6): d (S) -5-Fluoro-N 4 - (2- 1.38 (d, 3 H), 4.58 (q, 1 H), methyl-3-oxo-2 H, 4 H- 6.78 (m, 1H), 7.18 (m, benz [1,4] oxazin-6-yl) -247 1H), 7.38 (m, 3H), 7.57 N2- [3- (oxazole-5- + + (, 1H), 7.79 (m, 1H), 8.22 il) phenyl] -2,4- (m, 2H) purity: 90%; EM pyridine diamine (m / e): 433 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 - [2- (2- 1.93 (m, 2H), 3.58 (m, 2H), hydroxyethyl) -3-oxo- 4.62 (m, 1H), 6.88 (m, 2H, 4H-benz [1,4] oxazin-48 2H), 7.22 (m, 3H), 7.57 7-yl] -N2- [3- (oxazole-2- + + (m, 2H), 7.79 (m, 2H), 8.22 il) fepyl] -2.4- (m, 2H) purity: 99%; EM pyramindinapiine (m / e): 463 (MH +). 1 H NMR (DMSO-d 6): d 1.93 5-Fluoro-N 4 - [2- (2- (m, 2 H), 3.58 (m, 2 H), 4.62 (m, hydroxyethyl) -3-oxo-1 H), 6.71 (m, 2H), 6.95 (m, 2H, 4H-benz [1,4] oxazine-49 1 H), 7.51 (s, 1 H), 7.69 (m, 7-yl) -N 2 - [4- (oxazol- 5- + 2H), 7.69 (m, 2H), 8.20 (d, yl) phenyl] -2,4- 1H), 8.38 (s, 1H) purity: 99 p? Irrindindiamine%; MS (m / e): 463 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): dd (R) -5- Fluoro-N4- (2-1.38 (d, 3H), 4.58 (q, 1H), methyl-3-oxo-2H, 4H-6.88 (m, 1H), 7.22 (m, benz [1,4] oxazin- 6-yl) - 250 4H), 7.57 (m, 1H), 7.99 N2- [3- (oxazole-4 + (m, 2H), 8.12 (m, 2H) yl) phenyl] -2.4-purity : 95%; MS (m / e): 433 pyrimidinediamine (MH +). 1 H NMR (DMSO-d 6): dd (S) -5-Fluoro-N 4 - (2- 1.38 (d, 3 H), 4.58 (q, 1 H), methyl-3-oxo-2 H, 4 H ~ 6.88 (m, 1H), 7.22 (m, benz [1,4] oxazin-6-yl) -251 4H), 7.57 (m, 1H), 7.99 N2- [3- (oxazole-4 + + (m, 2H), 8.12 (m, 2H) yl) phenyl] -2.4- purity: 99%; MS (m / e): 433 pyrimidimidia (MH +). 1 H NMR (DMSO-d 6): d (R, S) -N 2 - (3.5-2.18 (s, 6H), 2.25 (m, 2H) Dimethylphen) -5-fluoro-3.75 (t, 2H) 4.58 ( q, 1H), N4-252 6.52 (d, 1H), 6.92 (dd, 2H), (tetrabidrofuran [2,3] - + 7.37 (m, 3H), 8.12 (d, 1H) 2H-benz [l, 4] oxazin-6- purity: 90%; MS (m / e): 406 yl) -2,4-p-methylindi-amine (MH +). 1 H NMR (DMSO-d 6): d N 4 - [3,4-Dihydro-2- (2- 1.88 (m, 2 H), 2.97 (m, 2 H), hydroxyethyl) -2 H, 4 H- 3.55 (m, 2 H) , 3.61 (s, 6H), benz [1,4] oxazin-6-yl] -253 4.08 (q, 1H), 6.02 (m, 1H), N2- (3,5-dimethoxyphenyl) - + + 6.58 ( d, 1H), 6.96 (, 5H), 5-fluoro-2,4- 8.02 (d, 1H) purity: 96%; pyrimidindiamine MS (m / e): 442 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (N- 2.62 (d, 3 H), 3.32 (s, 2 H), methylamino) carbonyl- 4.37 (s, 2 H), 6.60 (m, 1H), methylenexifem] -N4- (3-254 7.22 (m, 3H), 7.37 (m, 1H), oxo-2H, 4H- + 7.43 (m, 1H), 8.02 (m, 1H), benzo [l , 4] thiazin-6-yl) - 8.22 (d, 1H) purity: 94%; 2,4-pyriridinediamine MS (m / e): 455 (MH +). 1 H NMR (DMSO-d 6): d N 4 - [2,3-DiMdro-2- (2- 1.88 (m, 2 H), 2.18 (s, 6 H), Mdroxyethyl) -2 H, 4 H - 2.97 (m, 2 H) 3.58 (m, 2H), benz [1,4] oxazin-6-yl] - 4.09 (q, 1H), 6.19 (m, 1H), 55 N2- (3,5-dimethylphenyl) -5- 6.42 ( m, 1H), 6.58 (, 1H), + + fluoro-2,4-6.81 (, 2H), 7.22 (s, 2H), pyrimidinediamine 8.02 (d, 1H) purity: 97%; MS (m / e): 410 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3,5-Dimethoxyphenyl) -3.37 (s, 2H), 3.61 (s, 6H), 5-fluoro-N4- (3-oxo- 6.18 (m, 1H) , 6.75 (m, 2H), 56 2H, 4H-benzo [1,4] thiazine- 7.22 (, 2H), 7.43 (m, 1H), + 6-yl) -2.4- 8.22 (d, 1H) purity: 98%; pyrimidindiamine EM (m e): 428 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp_sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- (3-Chloro- 4- 3.47 (s, 2H), 3.88 (s, 3H), methoxyphenyl) -5-fluoro-7.08 (m, 1H), 7.25 (s, 2H), 257 N4- (3-oxo-2H, 4H- 7.42 (m, 2H), 7.78 (m, 1H), + benzo [1,4] thiazin-6-yl) - 8.22 (d, 1H) purity: 99%; 2,4-pyrimididiamine MS (m / e): 432 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (3,4-Diltidro-2 H, 4 H-2.67 (d, 3 H), 3.32 (m, 2 H), benzo [1,4] thiazin-6-yl) -5 - 4.30 (s, 2H), 4.37 (m, 2H), fluoro-N2- [3- (N- 6.45 (m, 1H), 6.88 (m, 1H), 258 methylamino) carbonyl- 6.96 (m, 2H) , 7.13 (m, 1H), + + methylenexife? NTJ-2,4- 7.23 (m, 2H), 8.02 (m, 2H) pyrimidinediaiae purity: 92%; MS (m / e): 441 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - [3- (N- 2.62 (d, 3 H), 3.11 (s, 3 H), methylamino) carbon-3.32 (s, 2 H), 4.37 (s, 2H), methylenexyphenyl] -N4- (4-6.60 (m, 1H), 7.22 (, 3H), 259 methyl-3-oxo-2H-7.37 (m, 1H), 7.43 (m, 1H), + benzo [ 1,4) thiazin-6-yl) -8.02 (m, 1H), 8.22 (d, 1H) 2,4-pyrimidinediamine purity: 95%; MS (m / e): 469 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3,5-Dimethoxyphenyl) - 3.11 (s, 3 H), 3.32 (s, 2 H), 5-fluoro-N 4 - (4-methyl-3- 3.58 (s, 6H), 6.18 (m, 1H), 260 oxo-2H- 6.75 (m, 2H), 7.32 (m, 3H), + benzo [1,4] thiazin-6-yl) - 7.63 (m, 2H), 8.22 (d, 1H) 2,4-p? Imidindiamine purity: 98%; MS (m / e): 442 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3-Benzothioamide) -5-fluoro-N 4 - (3-oxo- 4.58 (s, 2 H), 6.98 (m, 1 H), 2 H, 4 H -benz [1, 4] oxazin- 7.19 (m, 2H), 7.39 (m, 3H), 61 7.93 (m, 1H), 8.19 (d, 1H) 6-ü) -2.4- purity: 90%; MS (m / e): 411 piriimdindiamine (MH +). 1 H NMR (DMSO-d 6): 1.91 N 2 - (3-Benzothioamide) -5-fluoro-N 4 - [2- (2- (m, 2 H), 3.54 (m, 2 H), 4.63 (, 1 H), 6.98 ( m, 1H), hydroxyethyl) -3-oxo- 62 7.19 (m, 2H), 7.39 (m, 3H), 2H, 4H-bepz [1,4] oxazin- + 7.93 (m, 1H), 8.19 (d , 1H) 6-yl] -2.4- purity: 93%; MS (m / e): 455 pyrimid diamine (MH +). N2- (3,5-Dimethoxyphenyl 1 H NMR (DMSO-d 6): d N 4 - (dioxide-2-methyl-1.42 (d, 3 H), 3.63 (s, 6 H), 4.69 (q, 1 H), 6.14 (s) , 1H), 1, 1, 3-trioxo-4H-63 6.92 (, 2H), 7.72 (s, 2H), benzo [1,4] thiazin-6-yl) -5- + + 7.92 (m, 2H ), 8.27 (d, 1H) fluoro-2,4-purity: 99%; MS (m / e): 474 pdtrm'dindiamine (MH +).

No. Compound Name Physical Data Triptase Triptase Triplase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d N2- (3 , 5-Dimethylphenyl) -5- 1.42 (d, 3H), 2.18 (s, 6H), fluoro-N4- (2-methyl-4.72 (q, 1H), 6.64 (m, 1H), 264 l, l, 3-trioxo-2H, 4H- 7.21 (m, 2H), 7.72 (s, 2H), + + benzo [1,4] thiazin-6-yl) - 7.68 (, 2H), 8.27 (d, 1H) 2 , 4-pmr dmdiamine purity: 99%; MS (m / e): 442 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 2 - (indazole-6- 1.42 (d, 3H), 4.79 (q, 1H), il) -N 4 - (2-methyl-1, 1, 3 7.23 (m, 1H), 7.60 (m, 1H), 265 trioxo-2H, 4H- 7.77 (m, 1H), 7.82 (m, 3H), + + + bezo [l, 4] thiazin-6-yl) - 8.16 (m, 1H), 8.27 (d, 1H) 2,4-pyrimidinediamine purity: 94%; MS (m / e): 454 (MH +). 5-Fluoro-N 4 - (2-methyl-1 H NMR (DMSO-d 6): dl, 1,3-trioxo-2H, 4H-1.42 (d, 3H), 3.66 (s, 9H), benzo [1,4] ] thiazin-6-yl) - 4.70 (q, 1H), 7.04 (m, 2H), 266 N2- (3,4,5-7.72 (s, 2H), 7.72 (m, 3H), + + trimetoxifem) -2.4- 8.22 (d, 1H) purity: 96%; pyrimidinediamine MS (m / e): 504 (MH +). N2- (3,5-Dimethoxyphenyl) - N 4 - (2,2-dimethyl-1,1,3-CLEM: ret time 12.32 trioxo-4H-267 min purity: 100%; EM bepzo [1,4] thiazin -6-yl) -5- + fluoro-2,4- (m / e): 488 (MH4) pyrimidinediamine N2- (3,5-Dimethylfenyl) ~ N4- (2,2-dimethyl-l, l, 3 - LCMS: ret time 13.35 trioxo-4H- 268 min purity: 99%; MS (m / e): benzo [1,4] thiazin-6-yl) -5- + 456 (MH +) fluoro-2,4 - pyrimidinediamine N4- (2,2-dimethyl-l, 3-trioxo-4H-benzo [thiazine-CLEM: ret. time 11.28 269 6-yl) -5-fluoro-2- (3,4,5- min purity: 99%; MS (m / e): + trimethoxyphenyl) -2.4- 518 (MH +) pyrirnidinediamine N2- (3,5-Dimethoxyphenyl) -5-fluoro-N4r (2-methyl-3-CLEM: time ret 11.69 270 oxo-2H, 4H-min purity: 95%; MS benzo [1,4] thiazin-6-yl) - (me): 442 (MH +) 2,4-pyri-midindiamine N2- (3 , 5-Dimethylphenyl) -5- fluoro-N4- (2-methyl-3-CLEM: ret. Time: 12.12 71 oxo-2H, 4H-min purity: 98%; EM benzo [1,4] thiazin-6 il) - (m / e): 410 (MH +) 2,4-pyriridinediamine No. Compound Name Physical Data Triptase Triptase Triptase ip sik Com LD, LD, LD , llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 5-Fluoro-N4- (2-methyl-3-oxo-2H, 4H-CLEM: time ret. 10.44 benzo [1,4] thiazin-6-yl) - 272 min purity: 99%; MS (m / e): + N 2 - (3,4,5- 472 (MH +) trimethoxyphenyl) -2,4-pyrididinediamine N 4 - (2,2-Dimethyl-1,1,3-trioxo-4H-CLEM: time ret.10.49 273 benzo [1, 4] thiazin-6-yl) -5- min purity: 95%; EM + fluoro-N2- (indazol-6-yl) - (m / e): 468 (MH +) 2,4-? -irimidia diamine N4- (2,2-Dimethyl-l, l, 3-trioxo-4H-CLEM time ret .. 8.66 min 274 benzo [l, 4] thiazin-6-yl) -5- purity: 96%; MS (m / e): 468 fluoro-N 2 - (indazol-5-yl) - (MH +) 2,4-pyrimidinediamine N 4 - (2,2-Dimethyl-1, 3, 3-trioxo-4H-benzofl, 4 ] thiazin-6-yl) -5- CLEM: time ret. 10.16 275 fluoro-N2- [3- (N- min purity: 93%; MS + methylamino) carbonyl- (m / e): 515 (MH +) methyleneoxyphenyl] -2,4- pyrimidinediamine N2- (3-Chloro-4 methoxyphenyl) -N 4 - (2,2-CLEM: time ret. 12.66 dimethyl-1, 1,3-trioxo-4H-276 benzo [thiazin-6-yl) -5- min purity: 99%; MS + (m / e): 492 (MH +) fluoro-2,4-pyrimidmdiamine 5-Fluoro-N 2 - (indazol-6-yl) -N 4 - (2-methyl-3-oxo-CLEM: time ret. min 277 2H, 4H-benzo [1,4] thiazine-purity: 95%; MS (m / e): 422 + 6-yl) -2.4- (MH +) pyrimidinediamine 5-Fluoro-N2- (indazole- 5- il) -N 4 - (2-methyl-3-oxo-LCMS: ret time 8.23 min 278 2H, 4H-benzo [1,4] thiazine purity: 98%; MS (m / e): 422 6 -il) -2,4- (MH +) pyrimidindiamine 5-Fluoro-N 2 - [3- (N-methylamino) carboml-methyleneoxifeuyl] -N 4 - (2-CLEM: ret. time 9.51 min 79 methyl-3-oxo- 2H, 4H- purity: 96%; MS (m / e): 469 + (MH +) benzo [1,4] thiazin-6-yl) -2,4-pyrimidinediamine No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret. 11.77 N4- (2-methyl-3-oxo- 280 min purity: 97%; EM 2 H, 4 H -benzo [1,4] thiazine- + (m / e): 446 (MH +) 6-yl) -2, 4- pyrimidinediamine 5-Fluoro-N2- (3-hydroxyphenyl) -N4 ~ (3-oxo-CLEM: ret time 8.18 min 281 2H, 4H-benzo [1,4] thiazine- purity: 99%; / e): 384 + 6-yl) -2,4- (MH +) pMmidindiamine racemic-5-Fluoro-N2- (3-hydroxyphenyl) -N4- (2-CLEM: time lap 9.11 min 282 metü-3- oxo-2H, 4H- purity: 99%; MS (m / e): 398 benzofl, 4] thiazin-6-yl) - (MH +) 2,4-pyrimidinediamine racemic-N 4 - (2,2-Dimethyl-1,1,3-trioxo-4H-LCMS: time ret 9.89 min benzo [1, 4] thiazin-6-yl) -5-283 purity: 99%; MS (me): 444 fluoro-N2- [3- (MH +) hidoxyphenyl] -2,4-racemic pyrimidinediamine-5-Fluoro-N2- [3-doxyphenyl] -N4- (2-CLEM: time ret. 9.33 ruin methyl-l, l, 3-trioxo-284 purity: 97%; MS (m / e): 430 2H, 4H-benzo [1,4] thiazin- + (MH +) 6-yl) -2,4-pyrimidinediamine racemic-5-Fluoro-N2- [3- (N-methylamino) carbonyl-CLEM: time ret. 9.44 min methylenexifepil] -N4- (2-85 purity: 93%; MS (me): 501 methyl-1, 1, 3-trioxo- (MH +) 2H, 4H-benzo [1,4] thiazin-6-ü ) -2,4- racemic pyrimidinediamine-N2- (3-chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret. 11.68 N4- (2-metü-l, l, 3- 86 min purity: 95%; trioxo-2H EM, 4H- (m / e): 478 (MH +) benzo [1,4] thiazin-6-yl) - 2,4-? Mmidindiamine 5-Fluoro-N4- (3-oxo-2H, 4H-benzo [1,4] thiazine-CLEM: ret. Time 9.49 min 87 6-ü) -N2- (3,4, 5- purity: 99%; MS (m / e): 458 + trimethoxyphenyl) -2,4- (MH +) pyrimidindiami a No. Compound Name Physical Data Triptase Triptase Triptase ip sik Com LD, LD, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 5-Fluoro-N2- (indazol-5- CLEM: ret time 7.28 min ü) -N4- (3-oxo-2H, 4H-288 purity: 98% MS (m / e): 408 + benzo [1,4] thiazin-6-yl) - (MH +) 2,4-pyrimidinediamine N 2 - (3-Chloro-4-methoxyphenyl) -N 4 - (2,2- LCMS: time ret.12.45 dimethyl-3-oxo-4H-289 min purity: 97%; EM benzo [thiazin-6-yl) -5- (m / e): 460 (MH +) fh? Oro-2,4 - pyrimidinediamine N2- (3,5-dimethoxyphenyl) -N4- (2,2-dimethyl-3-oxo-CLEM: ret. time 12.81 290 4H-benzo [1,4] thiazin-6- min purity: 99%; EM + il) -5-fluoro-2,4- (m / e): 456 (MH +) pyrimidinediami to N 4 - (2,2-Dimethyl-3-oxo-4 H -benzo [1,4] thiazin-6 CL EM: ret time 13.44 291 il) -N2- (3,5-min purity: 99%; EM + dimethylphenyl) -5-fluoro- (m / e): 424 (MH +) 2,4-pyrimid diamine N4- (2,2- dimethyl-3-oxo-4H-benzo [1,4] thiazin-6-LCMS: ret time 11.86 292 ü) -5-fluoro-N2- (3,4,5-min purity: 99%; EM + trimethoxyphenyl) ) -2.4- (m / e): 486 (MH +) pyrimidinediamine N4- (2,2-Dimethyl-3-oxo-4H-benzo [1,4] thiazine-6-CMS: time ret. 10.39 293 ) -5-fluoro-N2- (3- min purity: 99%; EM + hydroxyphenyl) -2,4- (me): 412 (MH +) pyrimidinediamine N4- (2,2-Dimethyl-3-oxo- 4H- benzo [l, 4] thiazin-6-LCMS: time ret 10.04 ü) -5-fluoro-N2- [3- (N- 294 min purity: 97%; methylamino EM) carbonyl- + (m / e): 483 (MH +) methylenexyphenyl] -2,4-pyrimidiadiamine N4- (2,2-Dimethyl-3-oxo-4H-benzo [1,4] thiazin-6-CLEM: ret. Time 10.54 295 il) -5-fluoro -N2- (indazolimine purity: 96%; EM + + 6-ü) -2.4- (m / e): 436 (MH +) p? Imidindiamine racemic-5-Fluoro-N2- (3-fluoro-4-methoxyphenyl) -N4- (2-CLEM: time ret. 11.91 296 methyl-l, l, 3-trioxo-min purity: 96%; EM + 2H, 4H-benzo [1,4] thiazine- (m / e): 462 (MH +) 6-il) -2.4 - pyrimidindiamine Compound Name Physical Data Triptase Triptase Triptase f_sik LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (2,2-Dimethyl-1,1,3-trioxo-4H-CLEM: ret. Time 12.11 benzo [1,4] thiazin-6-yl) -5- min purity: 96%; MS + fluoro-N2- (3-fluoro-4- + (m / e): 476 (MH +) methoxyphenyl) -2,4-pyrir-dindiamine racemic-5-Fluoro-N2- (3-fluoro-4-methoxyphenyl) -N4- (2-LCMS: ret time 11.29 min purity: 98%; ME + methyl-3-oxo-2H, 4H- + (m / e): 430 (MH +) benzo [1,4] thiazin-6 -yl) - 2,4-pyrimidinediamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benzo [thiazin-6-yl) -5- CLEM: time ret. 12.14 fluoro-N2- (3-fluoro-4-purine purity: 99%; EM + + methoxyphenyl) -2,4- (m / e): 444 (MH +) pyrimidinediamine 5-Fluoro-N2- (3-fluoro- 4-methoxyphenyl) -N4- (3-CLEM: ret. Time 10.56 oxo-2H, 4H-min purity: 97%; MS + + benzo [1,4] thiazin-6-yl) - (m / e): 415 (MH +) 2,4-pyripd diarynin N 2 - (3,5-Dimethylphenyl) -5-fluoro-N 4 - (3 -oxo-CLEM: time ret 11.76 2H, 4H-benzo [1,4] thiazin-ruin purity: 98%; EM + + 6-yl) -2.4- (m / e): 396 (MH +) pyrim? imdiamine N2- (3,5-Dimethylphenyl) -5-fluoro-N4- (l, 1 , 3-trioxo-CLEM: ret time 10.72 2H, 4H-benzo [1,4] thiazimine purity: 96%; MS + 6-yl) -2.4- (m / e): 428 (MH +) pyrimidindiamine N2- (3,5-dimethoxyphenyl) -5- CLEM: time ret. 10.06 fluoro-N 4 - (1,1,3-trioxo-min purity: 95%; EM 2 H, 4 H -benzo [1,4] thiazin- + (m / e): 460 (MH +) 6-il) -2 , 4-pyrimiddmdiarmna N2- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret. 10.13 N4- (1, 1, 3-trioxo-2H, 4H-min purity: 97%; MS + benzo [1,4] thiazin-6-yl) - (m / e): 464 (MH +) 2.4 -pmmidmdiamine 5-Fluoro-N2- [3- (N-methylamino) carbonyl-methyleneoxyphenyl] -N4-CLEM: time ret. 8.40 min purity: 97%; MS (m / e): 487 (l, l, 3-trioxo-2H, 4H- + (MH +) benzo [1,4] thiazin-6-yl) -2,4-pyrirm ^ indiamin No. Compound Name Physical Data Triptase Triptase Triptase fp_sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 5-Fluoro-N2- (3,4,5-tri-methoxyphenyl) -N4-CLEM: time ret. 9.19 min 306 (1, 1, 3-trioxo-2H, 4H-purity: 95%; MS (m / e): 490 benzo [1,4] thiazin-6-yl) - (MH +) 2,4-pyrimidinediamine 5-Fluoro-N 2 - (indazol-6-yl) -N 4 - (1, 3-trioxo-CLEM: ret time 8.33 min 307 2 H, 4 H -benzo [1,4] thiazine purity: 91%; MS (m / e): 440 + 6-yl) -2.4- (MH +) pyrioiidindianiin 5-Fluoro-N2- (3-hydroxyphenyl) -N4- (l, l, 3-CLEM: time ret 8.07 min 308 trioxo-2H, 4H- purity: 96%; MS (m / e): 416 + benzo [1,4] thiazin-6-yl) - (MH +) 2,4-pyra? Idindiamine 5-Fluoro- N2- (3-fluoro-4-methoxyphenyl) -N4-CLEM: time ret. 9.74 min 309 (1, 1, 3-trioxo-2H, 4H-purity: 95%, MS (me): 448 + benzo [1,4] thiazin-6-yl) - (MH +) 7 -pyrimidmdiatninp 5-Fluoro -N2- (indazol-5-yl) -N4- (1, 1, 3-trioxo-CLEM: ret time 7.40 min 310 2H, 4H-benzo [1,4] thiazine-purity: 94%; / e): 440 + 6-yl) -2,4- (MH +) pyrimidinediamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benzo [1,4] thiazin-6-CLEM: time ret. 311 ü) -5-fluoro-N2- (l- min purity: 99%; EM + + methylindazol-6-yl) -2,4- (m / e): 450 (MH +) pyrirm ^ mdiamine Trifluoroacetate salt of N4- (2,2-Dimethyl-3-LCMS: ret time 10.54 oxo-4H-312 min purity: 100%; EM benzo [1,4] thiazin-6-yl) -5- (m / e): 436 (MH +) fluoro-N2- (indazol-6-yl) -2,4-pirm? Idindiamine N2-Chloro-5-fluoro-N4-CLEM: time ret. 5.58 min (3-oxo-2H, 4H-313 purity: 95%; MS (m / e): 311 benzo [1,4] thiazin-6-yl) -4- (MH +) racemic pyrimidinamine-N2-Chloro- 5- fluoro-N 4 - (2-methyl-3-CLEM: ret time 11.18 314 oxo-2H, 4H-min purity: 95%; EM + benzo [1,4] thiazin-6-yl) -4- ( m / e): 325 (MH +) pyrimidinamine N2-Chloro-5-fluoro-N4-CLEM: time ret. 10.03 (1, 1, 3-trioxo-2H, 4H-315 min purity: 95%; EM benzo [1,4] thiazin-6-yl) -4- (m / e): 343 (MH +) pyrimidinamine No. Compound Name Physical Data Triptase Triptase Triptase ip_sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T N2-Chloro-N4- (2,2, - dimethyl-3- oxo-4H-LCMS: ret time 12.29 316 benzo [l, 4] thiazin-6-yl) -5- min purity: 95%; MS fluoro-4-pyridinamine (m / e): 339 (MH +) racemic-N2-Chloro-5-fluoro-N4- (2-methyl-CLEM: time lap 10.16 317 l, l, 3-trioxo- 2H, 4H- rain purity: 96%; MS benzo [1,4] thiazin-6-yl) -4- (m / e): 357 (MH +) pyrimidinamine N2-Chloro-N4- (2,2-dimethyl- 1, 3-trioxo-4H-CLEM: ret. time 10.50 318 benzo [1,4] thiazin-6-yl) -5- min purity: 96%; MS fluoro-4-pyrirnidinamine (m / e): 371 (MH +) N4- [benzoxathiazin-3 (4H) -one-6-yl] 2-chloro-CLEM: time ret. 6.40 min 319 5-fluoro-4- purity: 99%; MS (m / e): 296 + pmmidfeamine (MH +) N2-Chloro-N4- (3.3-CLEM: ret time 12.20 dimethyl-1,4-benzoxazin- 320 min purity 99% MS (m / e): + 6-ñ) -5-fluoro-309 (MH *) pyrimidinamine 1H NMR (DMSO-d6): d 9.57 (bs, 1H), 9.21 (bs, 1H), 8.16 (d, J = 3.6 Hz, 1H) , 8.01 (d, J = 8.1 Hz, 1H), 7.75 (s, N2- (3,5-dimethoxyphenyl) -1H), 7.40 (t, J = 8.1 Hz, 1H), 5-fluoro-N4- (3 - 7.01 (d, J = 8.4 Hz, 1H), 6.91 324 trifluoromethoxyphenyl) - (d, J = 2.1 Hz, 2H), 6.09-6.06 2,4-pyrimidinediamine (m, 1H), 3.65 (s, 6H); 19 F NMR (282 MHz, DMSO-d6): -57.17, -163.27; LCMS: purity: 99%; MS (m / e): 425 (MH +) JH NMR (DMSO-d6): d 9.54 (bs, 1H), 9.12 (bs, 1H), 8.15 (dd, J = 1.8 and 3.6 Hz, 1H), N2- (3,5-Dimethylphenyl) -5- 7.96 (d, J = 8.1 Hz, 1H), 7.75 fluoro-N4- (3- (s, 1H), 7.41 (t, J = 8.1 Hz, 25 trifluoromethoxyphenyl) - 1H ), 7.01 (d, J = 8.1 Hz, 1H), + 2,4-? Irimidindiamine 6.55 (s, 1H), 2.18 (s, 6H); 19 F NMR (282 MHz, DMSO-d 6): -57.01, -163.96; CLEM: pu No. Compound Name Physical Data Triptase Triptase Triptase ip sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt * H NMR (DMSO-d6): d 10.83 ( bs, 1H), 9.49 (s, 1H), 9.11 (s, 1H), 8.13 (dd, J = 1.2 5-Fluoro-N2- (indol-6- and 3.3 Hz, 1H), 8.05 (d, J = il) -N4- (3- 8.1 Hz, 1H), 7.80 (d, J = 13.2 326 + trifluoromethoxyphenyl) - Hz, 2H), 7.40-7.32 (m, 2H), 2,4-pyrimidiamine 7.21-7.16 (m , 2H), 6.99-6.95 (m, 1H), 6.34-6.28 (m, 1H); 19F NMR (282 MHz, DMSO-d6): - H NMR (DMSO-d6): d 10.87 (bs, 1H), 9.61 (s, 1H), 5-Fluoro-N4- [I- (N- 9.46-9.43 (m, 1H), 8.08 (d, methylamino) carbonyl- J = 3.6 Hz, 1H), 8.04-7.98 indole-6-yl] -N2- [3- (N- (m, 1H), 7.40-7.25 ( m, 4H), 327 methylamino) carbon-7.02 (dd, J = 1.8 and 8.4 Hz, methylenexyphenyl) -2.4- 1H), 6.95-6.90 (m, 1H), pyrimidinediamine 6.77-6.70 (m, 2H), 6.38-6.35 (m, 1H), 4.39 (s, 2H), 2.62 (d, J = 4.8 Hz! H NMR (DMSO-d6): d 9.15 (bs, 1H), 9.11 (s, 1H), 8.07 ( d, J = 3.9 Hz, 1H), 7.37 (s, N2- (3, 5-dimethoxyphenyl) -2H), 6.89 (d, J = 1.81 Hz, N4- (3,5-dimethylphenyl) -5- 2H) , 6.68 (s, 1H), 6.05 (t, J = 328 fluoro-2.4- 2.1 Hz, 1H), 3.61 (s, 6H), + pyrimidimediamide 2.23 (s, 6H); 19F NMR (282 MHz, DMSO -d6): -163.60; LCMS: purity: 99%; MS (m / e): 369 (MH XH NMR (DMSO-d6): d 9.45 (s, 1H), 9.22 (s, 1H), 8.12 (d , N4- (3,5-Dimethylphenyl) -5- J = 3.9 Hz, 1H), 7.68-7.64 fluoro-N2- (3-methoxy-5- (m, 1H), 7.58-7.54 (m, 1H), 329 trifluoromethylphenyl) -2.4- 7.33 (s, 2H), 6.71 (s, 2H), + pi rirnidindiamine 3.69 (s, 3H), 2.23 (s, 6H); LCMS: purity: 99%; MS (m / e): 407 (MH +). * H NMR (DMSO-d6): d 10.11 (bs, 1H), 9.94 (bs, 1H), 8.25 (d, J = 4.8 Hz, 1H), 7.67 N4- (3,5-Dimethylphenyl) -5- ( s, 2H), 7.24 (s, 2H), 7.14 (s, fluoro-N4- (3-methyl-5-1H), 6.80 (s, 1H), 2.25 (s, 30 + trifluoromethylphenyl) -2.4- 3H), 2.21 (s, 6H); 19 F NMR pyrimidinediamine (282 MHz, DMSO-d6): -61.76, -161.10; LCMS: purity: 99%; MS (m / e): 390 (M +).

No. Compound Name Physical Data Triptase Triptase Triptase fp_sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 9.86 (bs, 1H), 9.42 (bs, 1H), 8.20 N2- (3,5-Dimethylphenyl) -5- (d, J = 4.2 Hz, 1H), 7.80-7.76 331 fluoro-N4- (3-methoxy-5- (m, 1H), 7.56-7.51 (, 1H), + trifluoromethylfeml) -2.4- 7.18 (s, 2H), 6.94 (s, 1H), pyrirnidmdiamine 6.59 ( s, 1H), 3.74 (s, 3H), 2.15 (s, 6H); LCMS: purity: 97%; MS (m / e): 407 (MH +). ? NMR (DMSO-d6): d 9.59 (bs, 1H), 9.24 (bs, 1H), 8.18 (d, J = 3.3 Hz, 1H), 7.84-7.68 N2- (3, 5-dimethoxyphenyl) - (m, 1H), 7.61-7.57 (m, 1H), 5-fluoro-N4- (3-methoxy-6.89 (d, J = 2.4 Hz, 3H), 6.06 332 5-trifluoromethylphenyl) - (t, J = 2.4 Hz, 1H), 3.77 (s, 2,4-pyrimidiamine 3H), 3.61 (s, 6H); 19 F NMR (282 MHz, DMSO-d 6): -61.85, -163.20; LCMS: purity: 97%; ? NMR (DMSO-d6): d 9.80 (bs, 1H), 9.72 (s, 1H), 8.25 (d, J = 3.3 Hz, 1H), 7.77-7.72 N2, N4-Bis (3-methoxy-5- ( m, 1H), 7.60-7.52 (m, 3H), trifluoromethylphenyl) -5- 6.92 (s, 1H), 6.75 (s, 1H), 333 + fluoro-2,4- 3.77 (s, 3H), 3.71 ( s, 3H); pyrimidiamine 19 F NMR (282 MHz, DMSO-d 6): -61.90, -161.82; LCMS: purity: 97%; MS (m / e): 477 (MH +). * H NMR (DMSO-d6): d 9.83 (bs, 1H), 9.72 (bs, 1H), 8.25 (d, J = 3.6 Hz, 1H), 7.81-7.68 5-Fluoro-N4- (3-methoxy) (m, 3H), 7.57-7.52 (m, 1H), 5-trifluoromethylphenyl) -7.06 (s, 1H), 6.96-6.91 (m, 334 N2- (3-methyl-5-1H), 3.75 (s, 3H), 2.26 (s, trifluoromethylphenyl) -2,4- 3H); 19 F NMR (282 MHz, pyruman-indiamine DMSO-d 6): -61.82, -162.02; LCMS: purity: 91%; MS (m / e): 461 (M! H NMR (DMSO-d6): d 9.67 (bs, 1H), 9.24 (bs, 1H), 8.17 5-Fluoro-N4- (3-methoxy- (d, J = 3.6 Hz, 1H), 7.84-7.78 5-trifluoromethylphenyl) - (m, 1H), 7.59 (s, 1H), 6.95- 335 N2- (3,4,5- 6.87 (, 3H), 3.74 (s, 3H), + trimethoxyphenyl) -2.4- 3.59 (s, 6H); 19F NMR (282 pyrididiamine MHz, DMSO-d6): -61.86, -163.40; LCMS: purity: 96%; MS (m / e ): 469 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T lH NMR (DMSO-d6): d 9.56 (s, 1H), 9.09 (s, 1H), 8.61 (s, 1H), 8.14 (d, J = 3.6 Hz, 1H), N2- (3-Chloro-4-hydroxy- 7.82-7.77 (m, 1H), 7.57 -7.53 5-methylphenyl) -5-fluoro- (m, 1H), 7.52-7.48 (, 1H), 336 N4- (3-methoxy-5-7.27-7.23 (m, 1H), 6.89 (bs, trifluoromethylphenyl) -2.4- 1H), 3.76 (s, 3H), 2.10 (s, pyrimidimethamine 3H); 19 F NMR (282 MHz, DMSO-d 6): -61.80, -164.13; CLM J H NMR (DMSO-d 6): d 9.74 (s, 1 H), 9.70 (s, 1 H), 8.25 (d, J = 3.6 Hz, 1 H), 7.77-7.71 N 2 - (3,5-Dichlorophenyl) -5- (m, 3H), 7.55-7.50 (m, 1H), fluoro-N4- (3-methoxy-5-7.03-7.01 (m, 1H), 6.95-6.93 337 trifluoromethylphenyl) -2.4- + (m, 1H), 3.79 (s, 3H); 19F pyrimidinediamine NMR (282 MHz, DMSO-d6): -61.78, -161.76; LCMS: purity: 96%; MS (m e): 448 (MH +). X H NMR (DMSO-d 6): d N 2 - [3.5-10.11 (bs, 1H), 9.82 (bs, 1H), Bis (hydroxymethylene) phenyl 8.26 (d, J = 4.2 Hz, 1H),] -5 -fluoro-N4- (3- 7.83-7.79 (m, 1H), 7.57-7.51 338 methoxy-5- (m, 1H), 7.34 (bs, 2H), 6.99- + trifluoromethylphenyl) -2,4-6.94 ( , 2H), 4.38 (s, 4H), pyrimidindiamine 3.74 (s, 3H); LCMS: purity: 92%; MS (m e): 439 (MH +). * H NMR (DMSO-d6): d 9.98 (bs, 1H), 9.66 (bs, 1H), 8.24 N2- (4-Chloro-3,5- (d, J = 4.2 Hz, 1H), 7.76-7.71 dimethylphenyl) -5-fluoro- (m, 1H), 7.56-7.52 (m, 1H), 339 N4- (3-methoxy-5-7.37 (s, 2H), 6.98-6.95 (m, trifluoromethylphenyl) -2, 4-1H), 3.75 (s, 3H), 2.20 (s, pyrimidinediamine 6H); LCMS: purity: 98%; MS (m / e): 442 (MH +). 1 H NMR (DMSO-d 6): d 9.27 (s, 1H), 9.18 (s, 1H), 8.10 (d, 1H, J = 3.9 Hz), 6.99 N2, N4-Bis (3.5- (d, 2H , J = 2.1 Hz), 6.92 (d, 340 dimethoxyphenyl) -5-fluoro-2H, J = 2.4 Hz), 6.21 (t, 1H, + + 2,4-? Mmidindiamine J = 2.1 Hz), 6.05 (t , 1H, J = 2.4 Hz), 3.68 (s, 6H), 3.62 (s, 6H); LCMS: purity: 100%; MS (m / e): 401 (MH +) No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 341 + purity: 100%; MS (m / e): 336 (M +). JH NMR (DMSO-d6): d 9.10 (s, 1H), 9.09 (s, 1H), 8.02 (d, N2- [3.5- 1H, J = 3.9 Hz), 7.44 (s, 2H), Bis (hydroxymethylene) - 7.28 (d, 1H, J = 3.0 Hz), 7.24 phenyl] -N4- (3,4-342 (d, 1H, J = 2.7 Hz), 6.86 (s, ethylenedioxypheni) -5- 1H) , 6.79 (d, 1H, J = 8.7 Hz), fluoro-2,4- 5.05 (t, 2H, J = 6 Hz), 4.39 pyrimidinediamine (d, 4H, J = 5.4 Hz), 4.22 (bs, 4H); LCMS: purity: 97 1 H NMR (DMSO-d 6): d 9.19 (s, 1 H), 9.15 (s, 1 H), 8.08 (d, 1 H, J = 3.6 Hz), 7.46 N 2 - [3,5- (s , 2H), 7.01 (d, 2H, J = 2.1 Bis (hydroxymethylene) - Hz), 6.86 (s, 1H), 6.21 (t, 343 phenyl] -N4- (3.5-1H, J = 1.8 Hz) , 5.03 (t, 2H, + dimethoxypheni) -5-fluoro-J = 5.4 Hz), 4.38 (d, 4H, J = 2,4-pyrnunidinediamine 5.4 Hz), 3.68 (s, 6H); LCMS: purity: 86%; MS (m / e): 401 (MH + * H NMR (DMSO-d6): d 10.55 (s, lH), 9.27 (bd, 1H), N2- [3.5- 8.97 (s, 1H), 8.04 ( d, 1H, 3.6 Bis (hydoxymethylene) phenyl] Hz), 7.44 (d, 2H, J = 1.2 Hz), -N4- (2,2-dimethyl-3-oxo- 344 7.39 (dd, 1H, J = 2.4 and 8.4 4H-benz [1,4] oxazin-6- + + Hz), 7.24 (d, 1H, J = 2.4 Hz), il) -5-fluoro-2,4- 6.88 (d, 1H, J = 8.7 Hz), 6.85 pyrimidinediamine (bs, 1H), 6.38 (s, 2H), 5.08 (t, 1H, J = 5.6 Hz), 4.93 (t * H NMR (DMSO-d6): d 9.26 (s, lH) , 9.15 (s, 1H), 8.07 (bd, 1H, J = 3.9 Hz), 7.79 N2- [3.5- (dd, 1H, J = 2.7 and 9 Hz), 7.74 Bis (hydroxymethylene) - (d, 1H, J = 2.7 Hz), 7.43 (s, 345 phenyl] -N 4 - (3-chloro-4-2H), 7.11 (d, 1H, J = 9 Hz), + methoxyphenyl) -5-fluoro-6.86 ( s, 1H), 5.06 (t, 2H, J = 2,4-pyriridinediamine 5.4 Hz), 4.38 (d, 4H, J = 5.4 Hz), 3.84 (s, 3H); CLEM: puri No. Compound Name Data Physic Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T lH NMR (DMSO-d6): d 9.50 (bs, 1H), 9.28 (s) , 1H), 8.16 N2- [3.5- (d, 1H, J = 3.6 H z), 8.05 (d, Bis (hydroxymethylene) -1H, J = 2.7 Hz), 7.93 (dd, 1H, 346 phenyl] -N4- (3.4- J = 2.7 and 9.0 Hz), 7.52 (d, 1H , dichlorophenyl) -5-fluoro- J = 8.7 Hz), 7.44 (s, 2H), 6.87 2,4-p-methylindyamine (s, 1H), 5.09 (t, 2H, J = 5.7 Hz), 4.41 (d, 4H ), J = 5.4 Hz); LCMS: purity: 97%; lH NMR (DMSO-d6): d 11.02 (s, 1H), 10.49 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.69 (d, 1H, J = 4.8 Hz), 9.53 4H -benz [1,4] oxazin-6- (s, 1H), 8.12 (d, 1H, J = 3.6 il) -N2- [l- (N- 347 Hz), 7.52 (d, 1H, J = 8.4 Hz), methylaminocarboni) - 7.38 (t, 1H, J = 2.7 Hz), 7.11 lindol-6-ü) -5-fluoro-2,4- (s, 1H), 6.81 (d, 1H, J = 2.4 pyridin-diamine) Hz), 6.72 (dd, 1H, J = 1.8 and 8.4 Hz), 6.59 (dd, 1H, J = 2 1 H NMR (DMSO-d6): d 11.01 (s, 1H), 10.44 (s, 1H), N2 - (l- 9.50 (s, 1H), 8.16 (d, 1H, J = Aminocarbonylindole-6- 3.6 Hz), 8.07 (d, 1H, J = 5.4 il) -N4- (2,2-dimethyl-3-) Hz), 7.52 (d, 1H, J = 8.4 Hz), 348 oxo-4H- 7.38 (t, 1H, J = 2.7 Hz), 6.73 benz [1,4] oxazin-6-yl) -5- (dd) , 1H, J = 1.5 and 8.4 Hz), fluoro-2,4- 6.54 (, 2H), 5.69 (d, 1H, J = pyripddindiamine 8.7 Hz), 2.93 (s, 2H), 1.29 (s, 6H); LCMS: purity: 95%; MS (m / e): 462 (MH +)? NMR (DMSO-d6): d 9.26 (bs, 1H), 9.20 (s, 1H), 8.10 N2- (4-Chloro-3) , 5- (d, 1H, J = 3.9 Hz), 7.48 (s, dimethylfeml) -N4- (3.5-2H), 6.94 (d, 2H, J = 2.4 Hz), 349 + dimethoxyphenyl) - 5-fluoro-6.23 (t, 1H, J = 2.4 Hz), 3.68 2,4-pyrimidinediamine (s, 6H), 2.20 (s, 6H); LCMS: purity: 92%; MS (m / e): 403 (MH +). X H NMR (DMSO-d 6): d 9.20 (s, 1 H), 9.05 (s, 1 H), 8.08 (d, N 4 - (3, 5-dimethoxyphenyl) -1 H, J = 3.6 Hz), 7.27 (s, 2 H) ), N2- (3,5-dimethylfeml) -5- 6.97 (d, 2H, J = 2.1 Hz), 6.51 50 + fluoro-2,4- (s, 1H), 6.21 (t, 1H, J = 1.8 + phenylalindymine amine), 3.67 (s, 6H), 2.15 (s, 6H); LCMS: purity: 96%; MS (m / e): 369 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt * H NMR (DMSO-d6): d 9.16 (s, 1H ), 9.96 (s, 1H), 8.05 (d, N4- (3,5-Dimethoxyphenyl) -1H, J = 3.3 Hz), 7.22 (d, 1H, N2- (3.4- J = 2.7 Hz), 7.06 (dd, 1H, J = 351 ethylenedioxyphenyl) -5- 2.4 and 8.7 Hz), 6.99 (d, 2H, J = + fluoro-2.4- 2.1 Hz), 6.65 (d, 1H, J = 8.7 Hz) , 6.20 (t, 1H, J = 2.1 Hz), 4.17 (s, 4H), 3.69 (s, 6H); LCMS: purity: 91%; M * H NMR (DMSO-d6): d 9.82 (bs, 1H), 9.58 (bs, 1H), 8.21 N2- (3,5-Dichlorophenyl) - (d, 1H, J = 3.6 Hz), 7.75 (bs) , N4- (3, 5-dimethoxyphenyl) -2H), 7.04 (t, 1H, J = 1.8 Hz), 352 5-fluoro-2,4-6.89 (d, 2H, J = 1.8 Hz), 6.27 pyrimidiamine ( t, 1H, J = 2.1 Hz), 3.67 (s, 6H); LCMS: purity: 95%; MS (m / e): 410 (MH +). * H NMR (DMSO-d6): d 9.47 (s, 1H), 9.31 (s, lH), 8.15 (d, N4- (3,5-dimethoxyphenyl) -1H, J = 3.6 Hz), 7.86 (s, 1H), 5-fluoro-N2- (3-methyl-5-79 (s, 1H), 6.98 (m, 3H), 353 trifluoromethylfem) -2.4-6.23 (t, 1H, J = 2.4 Hz), 3.68 pyrimidinediamine (s, 6H), 2.27 (s, 3H); LCMS: purity: 96%; MS (m / e): 423 (MH +). ? NMR (DMSO-d6): d 9.56 (s, 1H), 9.28 (s, 1H), 8.11 (d, 1H, J = 3.6 Hz), 7.76 (d, 2H, N2- (3,5-Dichlorophenyl) - J = 1.8 Hz), 7.18 (d, 1H, J = N4- (3.4-2.4 Hz), 7.13 (dd, 1H, J = 3.6 354 ethylenedioxyphenyl) -5- and 9 Hz), 6.98 (t, 1H , J = 1.8 + fluoro-2,4-Hz), 6.82 (d, 1H, J = 8.7 Hz), pyrimidiamine 4.21 (bs, 4H); LCMS: purity: 81%; MS (m / e): 407 (M * H NMR (DMSO-d6): d 9.53 (s, 1H), 9.33 (d, 1H, J = 1.5 Hz), 8.16 (d, lH, J = 3.6 Hz) , N4- (3,5-Dimethoxyphenyl 7.65 (d, 1H, J = 2.1 Hz), 6.98 5-fluoro-N2- (3-methoxy-355 (d, 2H, J = 2.1 Hz), 6.72 (bs, 5 -trifluoromethylphenyl) - + 1H), 6.22 (t, 1H, J = 2.4 Hz), 2,4-pyrj ™ dindiamine 3.72 (s, 3H), 3.69 (s, 6H), CLEM: purity: 96%, MS ( m / e): 439 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 9.47 (s, 1H), 9.23 (s, 1H), 8.09 (d, N4- (3.4-1H, J = 3.9 Hz), 7.67 (s, 1H), Ethylenedioxyphenyl) -5- 7.59 (s, 1H), 7.27 (d, 1H, J = 356 fluoro-N2- (3-methoxy-5-7.7 Hz), 7.18 (dd, 1H, J = 2.4 trifluoromethylphenyl) -2.4- and 8.4 Hz), 6.78 (d, 1H, J = 8.7 pyrimidmdiamine Hz), 6.78 (s, 1H), 4.21, bs, 4H), 3.72 (s, 3H); LCMS: purity: 90%; MS (m / e): H NMR (DMSO-d6): d 9.64 (s, 1H), 9.29 (s, 1H), 8.15 N2- (3,5-Dimethoxyfengine> (m, 2H), 7.62 (dd) , 1H, J = 2.4 5-fluoro-N4- [3,4- and 9 Hz), 7.39 (d, 1H, J = 8.7 357 (tetrafluoroethylenedioxy) - + Hz), 6.90 (d, 2H, J = 2.4 Hz ), fenüJ-2,4- 6.09 (t, 1H, J = 1.8 Hz), 3.66 pMmidindiamine (s, 6H), CLEM: purity: 97%, MS (m / e): 471 (MH +) 'H NMR (p. DMSO-d6): d 9.90 (bs, 1H), 9.56 (bs, 1H), 8.21 N2- (4-Chloro-3,5- (bd, 1H, J = 3.6 Hz), 8.06 (bs, dimethylphenyl) - 5-fluoro-1H), 7.57 (dd, 1H, J = 2.4 and N4- [3.4-358 9.0 Hz), 7.43 (d, 1H, J = 9.3 (tetrafluoroethylenedioxy) - Hz), 7.39 (s, 2H ), 7.06 (bs, phenyl] -2,4- 1H), .25 (s, 6H), CLEM: pyr? M ^ mydiamine purity: 97%, MS (m / e): 473 (MH +). * H NMR (DMSO-d6): d 9.60 (s, 1H), 9.32 (s, 1H), 8.16 (d, N2- [3.5-2H, J = 3.6 Hz), 7.70 (dd, 1H, Bis (Hdroxymethylene ) - J = 2.7 and 9 Hz), 7.47 (s, 2H), phenyl] -5-fluoro-N4- [3.4-359 7.40 (d, 1H, J = 9.0 Hz), 6.88 (tetrafluoroethylenedioxy) - ( bs, 1H), 5.11 (t, 2H, J = 5.4 phenyl] -2.4-Hz), 4.42 (d, 4H, J = 5.4 Hz); pir? iddindiamine CLEM: purity: 98%; MS (m / e): 471 (MH +). * H NMR (DMSO-d6): d 9.76 (s, 1H), 9.72 (s, 1H), 8.25 (d, N2- (3,5-Dichlorophenyl) -5- 1H, J = 3.6 Hz), 8.00 ( d, 1H, fluoro-N4- [3.4- J = 2.4 Hz), 7.74 (d, 2H, J = 360 (tetrafluoroethylenedioxy) - 1.8 Hz), 7.58 (dd, 1H, J = 2.4 phenyl] -2, 4- and 9.0 Hz), 7.44 (d, lH, J = 9.0 pyrimidinediamine Hz), 7.04 (t, 1H, J = 1.8 Hz); LCMS: purity: 98%; MS (m / e): 480 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase fp_sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T JH NMR (DMSO-d6): d 9.72 (s, 1H ), 9.64 (s, 1H), 8.23 (d, 5-Fluoro-N2- (3-methoxy-1H, J = 3.6 Hz), 8.07 (d, 1H, 5-trifluoromethylfenyl) - J = 2.4 Hz), 7.67 (bs, 1H), N4- [3,4-361 7.60 (dd, 1H, J = 2.4 and 9.3 (tetrafluoroethylenedioxy) - Hz), 7.54 (bs, 1H), 7.39 (d, phenyl] -2,4- 1H, J = 9 Hz), 6.75 (bs, 1H), pyrimidinediamine 3.75 (s, 3H); LCMS: purity: 97%: MS (m / e): 509 (MH +) 1 H NMR (DMSO-d 6): d 9.60 (s, 1H), 9.19 (s, 1H), 8.15 (d, N2- (3, 5-Dimethylphenyl) -5- 1H, J = 3.6 Hz), 8.12 (d, 1H, fluoro-N4- [3,4- J = 2.4 Hz), 7.60 (dd, 2.4 and 362 (tetrafluoroethylenedioxy) - 8.7 Hz) , 7.40 (d, 1H, J = 9 + phenyl] ~ 2.4-Hz), 7.22 (s, 2H), 6.56 (s, pyrimidinediamine 1H), 2.18 (s, 6H); LCMS: purity: 100%; MS (m / e): 439 (MH +). : H NMR (DMSO-d6): d 9.53 (s, 1H), 9.27 (s, 1H), 8.08 (d, N4- (3.4-1H, J = 3.6 Hz), 7.93 (d, 1H, Ethylenedioxyphenyl) ) -5- J = 2.4 Hz), 7.37 (dd, 1H, J = fluoro-N2- [3,4-363 2.4 and 9.3 Hz), 7.26 (d, 1H, J = + (tetrafluoroethylenedioxy) - 9 Hz) , 7.11 (dd, lH, J = 2.4 and phenyl] -2.4- 8.7 Hz), 6.80 (d, 1H, J = 8.4 pyrimidinediamine Hz), 4.22 (s, 4H); LCMS: purity: 96%; MS (m / e) J H NMR (DMSO-d 6): d 9.59 (s, 1 H), 9.37 (d, 1 H, J = 0.9 N 4 - (3,5-Dimethoxyphenyl) - Hz), 8.14 (d, 1 H, J = 2.4 Hz), 5-fluoro-N2- [3,4- 7.38 (dd, 1H, J = 2.7 and 9.3 364 (tetrafluoroethylenedioxy) - Hz), 7.27 (d, 1H, J = 9.0 Hz), + phenyl ] -2.4-6.91 (d, 2H, J = 2.4 Hz), 6.26 pyrimidinediamine (t, 1H, J = 2.4 Hz), 3.69 (s, 6H); LCMS: purity: 96%; MS (m / e): 471 (MH +). lH NMR (DMSO-d6): d 11.59 (s, 1H), 9.66 (s, 1H), 5-Fluoro-N2- [2- (N- 9.34 (s, 1H), 8.46 (d, 1H, J = methylamino) carbonyl- 4.8 Hz), 8.20 (d, 1H, J = 3.6 indole-7-yl] -N4- [3.4-65 Hz), 8.10 (d, 1H, J = 2.4 Hz), + (tetrafluoroethylenedioxy) ) - 7.91 (d, 1H, J = 7.2 Hz), 7.60 phenyl] -2,4- (dd, 1H, J = 2.7 and 9 Hz), 7.39 p? Imidindiamine (d, 1H, J = 9.0 Hz), 7.24 (d, 1H, J = 7.5 Hz), 7.06 (d, 1 No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion , 3pt: H NMR (DMSO-d6): d 9.70 (s, 1H), 9.60 (s, 1H), 8.22 (d, 5-Fluoro-N2- (3-methyl-5-1H, J = 2.4 Hz) , 8.07 (d, 1H, trifluoromethyl) -N4- [3, 4- J = 2.4 Hz), 7.87 (s, 1H), 7.70 366 (tetrafluoroethylenedioxy) - (s, 1H), 7.60 (dd, 1H, J = 2.1 + phenyl] -2.4- and 9 Hz), 7.41 (d, 1H, J = 9 pyrimidinediamine Hz), 7.04 (s, 1H), 2.31 (s, 3H), CLEM: purity: 100%, EM ( m / e): 493 (MH +). * H NMR (DMSO-d6): d 9.48 (s, 1H), 9.12 (s, lH), 8.11 (d, N2- (3.4-2H, J = 3.6 Hz), 7.59 (dd, 1H, Ethylenedioxy) phenyl) -5- J = 2.4 and 9 Hz), 7.39 (d, 1H, 36? fluoro-N4- [3,4- J = 9.3 Hz), 7.22 (d, 1H, J = + (tetrafluoroethylenedioxy) - 2.4 Hz), 6.99 (dd, 1H, J = 2.4 phenyl] -2,4- and 8.7 Hz), 6.70 (d, 1H, J = 9 pyrindene diamine Hz); LCMS: purity: 96%; MS (m / e): 469 (MH +). H NMR (DMSO-d6): d 11.70 (s, lH), 9.31 (s, 1H), 9. N4- (3,5-dimethoxyphenyl) -28 (s, 1H), 8.43 (d, 1H, J = 5-fluoro-N2- [2- (N- 4.8 Hz), 8.14 (d, 1H, J = 4.8 368 methyamino) carbonyl- Hz), 8.04 (dd, 1H, J = 0.9 and + + indol-7-il ] -2.4- 8.4 Hz), 7.19 (d, 1H, J = 7.5 pyrimidinediamine Hz), 7.03 (d, 1H, J = 2H, J = 2.4 Hz), 6.89 (t, 1H, J = 8.4 Hz) , 6.24 (t, lH, J = 2.4 Hz), lH NMR (DMSO-d6): d 10.57 (s, 1H), 9.35 (s, 1H), N2- (3-Chloro-5-9.27 (s, 1H ), 8.10 (d, 1H, J = methoxyphenyl) -N4- (2.2- 3.6 Hz), 7.47 (m, 1H), 7.25 dimethyl-3-oxo-4H- (dd, 1H, J = 2.7 and 8.7 Hz), 369 + benz [1,4] oxazin-6-yl) -5- 7.16 (d, 2H, J = 2.1 Hz), 6.87 fluoro-2,4- (d, 1H, J = 8.4 Hz), 6.49 (t, pyrimidindiamine 1H, J = 1.8 Hz), 3.66 (s, 3H), 1.40 (s, 6H); LCMS: purity: 10 JH NMR (DMSO-d6): d 9.31 (s, 1H), 9.21 (s, 1H), 8.08 (d, N2- (3-Chloro-5-1H, J = 3.9 Hz), 7.48 (t, 1H, methoxyphenyl) -N4- (3, 4- J = 1.8 Hz), 7.20 (m, 3H), 70 ethylenedioxyphenyl) -5-6.80 (d, 1H, J = 8.4 Hz), 6.49 + fluoro- 2.4- (t, 1H, J = 2.4 Hz), 4.21 (s, pyrimid diaauna 4H), 3.67 (s, 3H); LCMS: purity: 95%; MS (m / e): 403 (MH +).

No. Name of Compound Physical Data Triptase Tftasa Tftasa f sik Com LD, LD, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 11.27 (s, 1H), 9.25 (s, 2H), 5-Fluoro-N4- (3.4- 8.43 (d, 1H, J = 4.5 Hz), 8.09 methylenedioxyphenyl) -N2 - (d, 1H, J = 3.9 Hz), 8.01 (d, [2- (N- 371 1H, J = 7.8 Hz), 7.51 (d, 1H, metüamino) carbon- J = 2.1 Hz), 7.6 (m , 2H), 7.04 indole-7-yl] -2.4- (d, 1H, J = 1.8 Hz), 6.92 (t, pyrimidindiamiaa 1H, J = 7.8 Hz), 6.84 (d, 1H, J = 8.1 Hz ), 6.01 (s, 2H), 2.81: H NMR (DMSO-d6): d 9.20 (s, 1H), 9.10 (s, 1H), 8.05 (d, 1H, J = 3.6 Hz), 7.44 (d, 1H, N2- (3,5-dimethoxyphenyl) - J = 2.1 Hz), 7.16 (dd, 1H, J = 5-fluoro-N4- (3.4-37.2 2.1 and 8.4 Hz), 6.93 (d, 2H, J = + methylenedioxyphenyl) -2.4- 2.4 Hz), 6.84 (d, 1H, J = 8.4 pyrimidinediamine Hz), 6.04 (t, 1H, J = 2.1 Hz), 5.99 (s, 2H), 3.64 (s, 6H); LCMS: purity: 89%; M J H NMR (DMSO-d 6): d 9! 49 (s, 1 H), 9.30 (s, 1 H), 8.10 (d, 1 H, J = 3.6 Hz), 9.67 (bs, 5-Fluoro-N 4 - (3 , 4-1H), 7.58 (bs, 1H), 7.40 (d, methylenedioxyphenyl) -N2- 1H, J = 1.8 Hz), 7.11 (dd, 1H, 373 (3-methoxy-5- J = 1.8 and 8.4 Hz ), 6.84 (d, 1H, trifluoromethylphenyl) -2.4- J = 8.4 Hz), 6.70 (bs, 1H), pyrirnidindiamine 6.99 (s, 2H), 3.73 (s, 3H); LCMS: purity: 97%; MS (m / * H NMR (DMSO-d6): d 9.46 (s, 1H), 9.29 (s, 1H), 8.10 (d, 5-Fluoro-N4- (3.4-1H, J = 3.6 Hz) , 7.78 (bs, methylenedioxyphenyl) -N2- 1H), 7.39 (d, 1H, J = 2.1 Hz), 374 (3-methyl-5-7.10 (1H, J = 2.4 and 8.4 Hz), trifluoromethylphenyl) -2, 4- 6.99 (bs, 1H), 6.85 (d, 1H, J = pyrinidinediamine 8.4 Hz), 5.99 (s, 2H), 2.28 (s, 3H), CLEM: purity: 99%, MS (m / e): 407 (MH +). LH NMR (DMSO-d6): d 9.59 (s, 1H), 9.36 (s, 1H), 8.12 (d, 1H, J = 3.9 Hz), 7.74 N2- (3,5-Dichlorophenyl) -5- (d, 2H, J = 2.1 Hz), 7.30 (d, fluoro-N4- (3.4-1H, J = 2.1 Hz), 7.06 (dd, 1H, 375 methylenedioxyphenyl) -2.4- J = 2.4 and 8.4 Hz), 6.97 (t, 1H, + pinrmidmdiamine 2.1 Hz), 6.88 (d, 1H, J = 8.4 Hz), 6.00 (s, 2H), CLEM: purity: 94%, MS (m / e ): 393 (M + No. Compound Name Physical Data Triptase Tftase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IE, 3pt IgE, 8pt Ion, 3pt * H NMR (DMSO-d6): d 9.18 (bs, 1H), 9.03 (s, 1H), 8.04 (d, 1H, J = 3.9 Hz), 7.43 (d, N2- (3,5-Dimethylphenyl) -5- 1H, J = 2.1 Hz), 7.24 (s, 2H), flu gold-N4- (3.4-37.6 7.11 (dd, 1H, J = 2.1 and 8.4 + methylenedioxyphenyl) -2.4-Hz), 6.85 (d, 1H, J = 8.4 Hz), pyrinidinediamine 6.50 (bs, 1H ), 5.98 (s, 2H), 2.16 (s, 6H); LCMS: purity: 87%; MS (m e): 353 (MH +). N2- (4-Chloro-2,5-dimethoxyphenyl) -N4- (3-CLEM: purity: 100%; EM 377 chloro-4-methoxyphenyl) -5- + (m / e): 439 (M +). fluoro-2,4-pyriridinediamine? NMR (DMSO-d6): d 10.63 (s, 1H), 10.05 (s, 1H), P-9.62 (s, 1H), 8.15 (d, 1H, J = toluenesulfonic acid of N2- 4.8 Hz), salt of the acid, 7.66 (bs, 1H), 7.44 (3-Chloro-4-methoxyphenyl) - (dd, 2H, J = 1.8 and 8.7 Hz), 378 N4- (2,2-dimethyl-3-oxo- 7.35 (bd, 1H , J = 9 Hz), 7.20 4H-benz [1,4] oxazin-6- (dd, 1H, J = 2.1 and 8.7 Hz), il) -5-fluoro-2,4-7.10 (bd, 2H, J = 7.5 Hz), pyridine diamine 7.02 (d, 1H, J = 9 Hz), 6.89 (, l 'H NMR (DMSO-d6): d 9.24 (s, 1H), 8.05 (d, 1H, J = 3.9 N2- (4-Chloro-2.5-Hz), 7.87 (s, 1H), 7.70 (s, dimethoxyphenyl) -N4- (3,4- 1H), 7.17 (d, 1H, J = 2.4 Hz), 379 ethylenedioxyphenyl) -5- 7.06 (m, 2H), 6.74 (d, 1H, J = + fluoro-2,4- 8.7 Hz), 4.21 (s, 4H), 3.79 (s, pyripndindindiamine 3H), 3.54 (s) , 3H); LCMS: purity: 100%; MS (m / e): 433 (MH +). N2- (4-Chloro-2,5-dimethoxyphenyl) -N4- (3,5-CLEM: purity: 100%; EM 380 + dimethoxyphenyl) -5-fluoro- (m / e): 435 (MH +). 2,4-pyrimidinediamine? NMR (DMSO-d6): d 9.36 (s, 1H), 8.25 (d, 1H, J = 1.8 N4- (3,5-Dimethoxyphenyl) - Hz), 8.11 (d, lH, J = 3.9 Hz), 5-fluoro-N2- (2-7.57 (m, 3H), 6.99 (m, 2H), 381 methoxycarbonylbenzo- + + 6.26 (t, lH, J = 2.1 Hz), 3.88 furan-5-yl) -2, 4- (s, 3H), 3.69 (s, 6H); LCMS: pyrimidinediamine purity: 92%; MS (m / e): 439 (MH +). N2- (2- Carboxybenzofuran-5 LCMS: purity: 91%; MS 382 il) -N4- (3,5- (m / e): 425 (MH +). Dimethoxyphenyl) -5-fluoro- 2,4- pyrimidindiamine No. Compound Name Physical Data Triptase Tftase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 11.85 (s, 1H), 9.31 (s, 1H), 9.26 ( s, 1H), 8.16 (d, 1H, J = N2- (2-Carboxyindol-7- 3.6 Hz), 8.12 (d, 1H, J = 8.1 il) -N4- (3.5-Hz), 7.22 ( d, 1H, J = 8.1 Hz), 383 + dimethoxyphenyl) -5-fluoro-7.02 (d, 2H, J = 2.1 Hz), 6.91 2,4-pyrimidinediamine (t, 1H, J = 7.8 Hz), 6.25 ( s, 1H) 3.70 (bs, 6H); LCMS: purity: 80%; MS: 424 (MH +)! H NMR (DMSO-d6): d 11.52 (s, 1H), 9.30 (bs, 1H), N 4 - (3,5-Dimethoxyphenyl) - 9.27 (s, 1H), 8.14 (d , 1H, J = 5-fluoro-N2- [2- (N-2- 3.6 Hz), 8.04 (m, 1H), 7.22 hydroxyethyl-N- (d, 1H, J = 8.4 Hz), 7.03 (m, 384 + + + methylamino) carbonyl- 2H), 6.90 9m, 2H), 6.23 9bs, indole-7-yl] -2,4- 1H), 3.68 (s, 6H), 3.64 (bs, pyrimidindiainine 4H), 3.20 (s, 3H); LCMS: purity: 94%; MS (m / e): 481 (MH +). 1 H NMR (CDCD): d 7.50 N 4 - (3,4- (bs, 1H), 7.30 (m, 2H), 6.91 Ethylenedioxyphenyl) -5- (bd, 1H, J = 7.2 Hz), 6.73 (m, fluoro -N4-methyl-N2- [3- 5H), 4.49 (s, 2H), 4.31 (s, 385 + (N-methylamino) carbonü- 4H), 3.60 (s, 3H), 2.92 (d, methyleneoxyphenyl) - 2.4-3H, J = 4.5 Hz); : CMS: p? ± nidindiamine purity: 97%, MS (m / e): 440 (MH +) 1 H NMR (CDC 13): d 7.94 (d, 1 H, J = 5.1 Hz), 7.50 (bd, N 4 - (3 , 4-1H), 6.90 (d, 1H, J = 9 Hz), Ethylenedioxyphenyl) -N2-6.83 (s, 1H), 6.73 (m, 3H), 386 (3,5-dimethoxyphenyl) -5-6.66 ( d.1H, 2.4 Hz), 4.31 + + fluoro-N4-methyl-2,4- (m, 4H), 3.80 (s, 3H), 3.79 pyrimidinediamine (s, 3H), 3.60 (s, 3H); LCMS: purity: 90%, MS: 413 (MH +). 1 H NMR (CDC13): d 7.50 (bd, 1H), 7.40 (s, 1H), 7.27 N2- (3,5-Di-ethylphenyl) - (m, 1H), 6.90 (bdd, 1H), 6.81 N4- ( 3.4- (m, 1H), 6.77 (d, 2H, J = 2.4 387 ethylenedioxyphenyl) -5- Hz), 6.70 (dd, 1H, J = 2.7 and + fluoro-N4-methyl-2,4- 8.7 Hz), 4.30 (s, 4H), 3.50 (s, pyrimidindiarnine 3H), 2.32 (s, 6H); LCMS: purity: 94%, MS (m / e): 381 (MH +).

No. Name of Compound Physical Data Triptase Tftase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.60 (s, 1H) , 9.21 (s, 1H), N2- (3, 5-dimethoxyphenyl) - 7.94 (d, 1H, J = 6.0 Hz), 7.01 N4- (2,2-dimetii-3-oxo- (d, 2H, J = 1.2 Hz), 6.88 (m, 388 4H-benz [1,4] oxazin-6- 2H), 6.75 (d, 1H, J = 2.4 Hz), il) -5-fluoro-N4-metü-6.05 ( t, 1H, J = 2.4 Hz), 3.60, 2,4-pyrimidinediamine (s, 6H), 3.41 (s, 3H), 1.34 (s, 6H); LCMS: purity: 92%, MS (m / e): 454 (MH +). * H NMR (DMSO-d6): d 11.63 (s, lH), 9.25 (d, lH, J = N4- (3,5-dimethoxyphenyl) - 7.8 Hz), 8.14 (d, 1H, J = 3.6 N2- [2- (N, 1-dimethyl-2 Hz), 8.02 (d, 1H, J = 8.1 Hz), hydroxyethylamino) -389 7.53 (s, 1H), 7.19 (d, 1H, J = carbonylindole-7- il] -5- 7.5 Hz), 7.14 (s, 1H), 7.04 (s, fluoro-2,4-2H), 6.89 (t, 1H, J = 7.5 Hz), pyrimidinediamine 6.23 (s, 1H), 4.94 (t, 1H, J = 6.3 Hz), 3.69 (s, 6H), 1H NMR (CDC13): d 7.85 (d, 1H, J = 4.8 Hz), 6.86 (d, 2-Chloro-N4- (3, 4-1H, J = 8.4 Hz), 6.73 (d, 1H, ethylenedioxyphenyl) -5- 390 J = 2.7 Hz), 6.60 (dd, 1H, J = fluoro-N4-methyl-4- 2.7 and 8.1 Hz); LCMS: pyriodynamine purity: 100%, MS (m / e): 296 (M +). 1 H NMR (CDC13): d 7.95 (d, 1H, J = 6.4 Hz), 7.67 (bs, N2- (3,5-Dimethylphenyl) -5- 1H), 7.21 (s, 2H), 6.96 (s, fluoro) -N4-methyl-N4- (3-1H), 6.87 (dd, 1H, J = 2.4 and oxo-2.2.4- 8.7 Hz), 6.78 (d, 1H, J = 2.4 391 trimethylbenz [1.4] ] oxazin-Hz), 6.72 (s, 1H), 3.55 (s, + + 6-yl) -2.4- 3H), 3.32 (s, 3H), 2.30 (s, pyrimidinediamine 6H), 1.53 (s, 6H); LCMS: purity: 92%, MS (m / e): 436 (MH +). 1 H NMR (CD30D): d 7.77 N2- (3-Chloro-4- (d, 1H, J = 2.4 Hz), 7.75 (bd, methoxyphenyl) -5-fluoro-1H), 7.34 (dd, 1H, J = 2.7 and N4-methyl-N4- (3-oxo- 9.3 Hz), 7.05 (d, 1H, J = 1.8 392 2.2.4-Hz), 6.95 (m, 3H), 4.62 (s, trimethylbenz [1 , 4] oxazin-3H), 3.83 (s, 3H), 3.51 (s, 6-yl) -2,4- 3H), 1.48 (s, 6H); LCMS: pyrirm ^ mdiamine purity: 94%, MS (m / e): 472 (M +).

No. Compound Name Physical Data Triptase Triptase Tftasa f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (CD30D): d 7.78 N2- (3.5- Dimethoxyphenyl) - (d, 1H, J = 8.4 Hz), 7.07 (bs, 5-fluoro-N4-methyl-N4- 1H), 6.96 (bs, 2H), 6.87 (d, (3-oxo-232.4 - 2H, J = 2.4 Hz), 6.10 (t, 1H, 393 + + trimethylbenz [1, 4] oxazin- J = 2.4 Hz), 3.70 (s, 6H), 3.54 6-il) -2.4- ( s, 3H), 3.32 (s, 3H), 1.48 (s, pyrimidinediamine 6H); LCMS: purity: 97%, MS (m e): 468 (MH +). N2- (3-Chloro-4-methoxyphenyl) -N4- (2,2-dimethyl-3-oxo-4H-LCMS: purity: 93%, MS 394 + benz [1,4] oxazin-6-yl) - 5- + (m / e): 351 (MH +). fluoro-N4-methyl-2,4-pyrimidindiamine 395 + + 396 + + 397 + + + pyrMdmdiamine N4- (3,5-dimethoxyphenyl) -5-fluoro-N4-methyl-N2- [3- (N-CLEM: purity: 94%, MS 398 + methylamino) carbonyl- (m / e) : 442 (MH +). methylenexyphenyl] -2,4- pyrimidinediamine N 4 - (3,5-dimethoxyphen) - N 2 - (3,5-dimethylphenyl) -5- LCMS: purity: 92%, EM 99 + + fluoro-N 4 -methyl-2,4 - (m / e): 382 (MH +). pyrimidinediamine 1H NMR (DMSO-d6): d 9.23 (s, 1H), 7.97 (d, 1H, J = N2, N4-Bis (3.5- 5.1 Hz), 7.01 (d, 2H, J = 1.8 dimethoxyphenyl) -5-fluoro-Hz), 6.45 (d, 2H, J = 1.2 Hz), 00 N4-methyl-2,4- 6.34 (bt, 1H), 6.05 (bt, 1H), pyrimidmdiamine 3.72 (s, 6H) 3.68 (6H), 3.45 (s, 3H); LCMS: purity: 95%, MS (m / e): 415 (MH +).

No. Triptasa f sik Com LD, llpt CMC, Iono, 3pt 401 + 402 403 (s, 1H), 8.08 (d, 1H, J = 6.00 N2- (3-Chloro-4 Hz), 7.89 (d, 1H, J = 5.1 Hz), methoxyphenyl) -N4- (3.5-7.47) (dd, 1H, J = 2.7 and 9.3 Hz), 404 dimethoxyphenyl) -5-fluoro-7.08 (d, 1H, J = 9.0 Hz), 6.53 (d, N4-methyl-2,4-2H, J = 1.8 Hz), 6.46 (t, 1H, J = pyrimidinediamine 2.1 Hz); LCMS: purity: 92%, 419 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (4-Chloro-3- 9.30 (s, 1 H), 9.03 (s, 1 H), methoxyphenyl) -N 4 - (3, 5- 8.07 (d, 1 H, J = 4.2 Hz), 7.48 405 dimethoxyphenyl) -5-fluoro- (d, 1H, J = 2.1 Hz), 7.37 (dd, + N4-methyl-2,4- 1H, J = 2.4 and 8.4 Hz), 7.24 (s) , pyrimidinediamine 2H); LCMS: purity: 91%, MS (m / e): 419 (M +). 1 H NMR (DMSO-d 6): d 11.71 N 4 - (3,5-Dimethoxyphenyl) - (s, 1 H), 9.39 (s, 1 H), 8.44 (bd, 5-fluoro-N 4 -methyl-N 2 - 1 H, J = 4.8 Hz), 8.02 (m, 2H), [2- (N- 7.20 (d, 1H, J = 7.5 Hz), 7.04 (d, 406 methyamino) carbonyl- 1H, J = 2.1 Hz), 6.93 (1 , 1H, J = + indole-7 ~ il] -2.4- 7.8 Hz), 6.47 (d, 2H, J = 2.1 Hz), pyrimidinediamine 6.41 (t, lH, J = 2.1 Hz), 3.72 (s, 6H), 3.46 (s, 3H), 2.81 (d, 3H, 1H NMR pMSO-d6): d 8.07 (d, 1H, J = 2.7 Hz), 7.69 (m, 2-Chloro-N4- [3-chloro -4- 1H), 7.45 (, 1H), 6.95 (d, 1H, 407 (ethoxycarboml-1,1- J = 9 Hz), 6.92 (bs, 1H), 4.28 (q, dimethylmethyleneoxy) f enyl] - 5 -fluoro-4- 2H, J = 6.9 Hz), 1.62 (s, 6H), 1.31 (t, 3H, J = 7.2 Hz); LCMS: pyrimidineam purity: 85%; MS (m / e): 388 (M +).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- [3-Chloro-4-1H NMR (CD30D): d 7.91 (d, 1H, (ethoxycarbonyl-1,1- J = 3.6 Hz), 7.74 (d, 1H, J = 2.7 Hz), dimethylmethyleneoxy) phenyl 7.66 (dd, 1H, J = 2.7 and 8.7 Hz), 6.91 408] -N2- (3.5- (d, 1H, J = 9 Hz), 6.789d, 2H, J = 2.1 + dimethoxyphenyl) -5-Hz), 6.12 (t, 1H, J = 2.1 Hz), 4.26 (q, fluoro-2,4-2H, J = 6.9 Hz), 3.71 (s, 6H), 1.59 (s, pyrimidinediamine 6H), 1.29 (t, 3H, J = 7.2 Hz); LC 1 H NMR (DMSO-d 6): d 13.15 N 4 - [3-Chloro-4- (bs, 1 H), 9.38 (s, 1 H), 9.18 (s, (hydroxycarbonyl-1,1-1 H), 8.10 (d , 1H, J = 3.9 Hz), dimethylmethyleneoxy) phenyl 7.93 (s, 1H), 7.84 (dd, 1H, J = 2.7 409] -N2- (3.5- and 9.3 Hz), 7.77 (d, 1H, J = 2.7 + dimethoxyphenyl) -5- Hz), 6.91 (, 3H), 6.07 (t, 1H, fluoro-2,4- J = 2.1 Hz), 3.65 (s, 6H), 1.52 (s, pyrimidinediamine 6H); LCMS: purity: 90%; MS (m 1 H NMR (DMSO-d 6): d 9.36 (s, N 4 - [3-Chloro-4- 1 H), 9.17 (s, 1 H), 8.08 (d, 1 H, J = (ethoxycarbonyl- 1,1- 3.6 Hz), 7.78 (d, 1H, J = 2.7 Hz), 410 dimethylmethyleneoxy) phenyl 7.75 (d, 1H, J = 2.1 Hz), 7.70 (dd,) -N2- (3-chloro-4-1H, J = 3.0 and 9.3 Hz), 7.44 (dd, methoxyphertil) -5-fluoro-1H, J = 2.7 and 9.0 Hz), 6.99 (d, 2,4-pyripindindiamine 1H, J = 9.0 Hz), 6.88 (d, 1H , J = 9.0 Hz), 4.20 (q, 2H, N4- (3,4-Ethylenedioxyphenyl) -5- LCMS: purity: 91%, MS (m / e): 411 fluoro-N4-methyl-N2- [3 - 420 (MH +) - (oxazol-5-yl) phenyl] -2,4- p midindiamine 1 H NMR (DMSO-d 6): d 9.61 (s, 1 H), 8.57 (s, 1 H), 8.17 (s, 1 H) ), 9.97 N4- (3.4- (d, 1H, J = 6.0 Hz), 7.70 (bd, 1H, J = Ethylenedioxyphenyl) -5- 4.8 Hz), 7.52 (bd, 1H, J = 7.8 Hz), 412 fluoro-N 4 -methyl-N 2 - [3- (oxazol-2-yl) phenyl] -2,4-738 (d, 1H, J = 8.1 Hz), 7.33 (s, 1H), 6.79 (m, 3H ), 4.24 (s, 4H), 3.44 (s, pyrimidinediamine 3H), LCMS: purity: 92%, MS (m / e): 420 (1 H NMR (DMSO-d 6): d 9.15 (s, N 4 - (3 , 4-1H), 8.97 (s, 1H), 8.02 (d, 1H, J = dimethoxyphenyl) -N2- 3.9 Hz), 7. 24 (, 4H), 6.88 (d, 413 (3,5-dimethylphenyl) -5- 1H, J = J = 8.4 Hz), 6.48 (d, 1H), + fluoro-2,4- 3.73 (s, 3H) ), 3.65 (s, 3H), 2.12 pmmidindiamine (s, 6H); LCMS: purity: 97%, MS (m / e): 369 (MH +). 1 H NMR (DMSO-d 6): d 9.17 (s, N 2 - (3.5 - 1 H), 9.05 (s, 1 H), 8.03 (d, 1 H, J = 3.9 Dimethoxyphenyl) - N 4 - Hz), 7.32 (dd) , 2.4 and 8.7 Hz), 124 (d, 414 (3, 4-dimethoxypheni) -5- 1H, J = 2.4 Hz), 6.92 (d, 2H, J = 2.4 + fluoro-2,4-Hz), 6.85 (d, 1H, 8.4 Hz), 6.03 (t, pmmidincüariiina 1H, J = 2.1 Hz), 3.73 (s, 3H), 3.66 (s, 3H), 3.60 (s, 6H); LCMS: purity: 96 o. Compound Name Physical Data Tftasa Tftasa Triptase f_syk om LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 415 N 4 - (3,4-dimethoxyphenyl) -1 H NMR (DMSO-d 6): d N 2 - [2- 11.89 (s, 1 H), 9.25 (s, 1 H), (ethoxycarbonyl) indole-7- 9.21 (s, 1H), 8.10 (d, 1H, ü) -5-fluoro-2,4- J = 3.9 Hz), 8.87 (s, 1H), 8.73 pyrimidinediamine (m, 3H), 7.11 (d, 1H, J = 2.1 + Hz), 6.88 (m, 2H), 4.32 (q, 2H, J = 3.9 Hz), 3.76 (s, 3H), 3.66 (s, 3H), 1.34 (q, t, 3H, J = 3.9 Hz) LCMS: purity: 93% 416 N4- (3.4-1H NMR (DMSO-d6): d Ethylenedioxypheni) -5- 9.59 (s, 1H), 8.05 (s, 1H), fluoro-N4-methyl-N2 - [4- 7.96 (d, 1H), J = 5.7 Hz), 7.80 (oxazol-2-yl) phenyl] -2,4- (bs, 4H), 7.27 (s, 1H), 6.85 pirinn ^ indiamina ( m, 2H), 6.78 (dd, 1H), 4.52 (s, 4H), 3.41 (s, 3H), 3.31 (s, 3H); LCMS: purity: 91%, MS (m / e): 420 (MH +). 417 2-chloro-N 4 - (3,4- 1 H NMR (DMSO-d 6): d-dimethoxyphenyl) -5-fluoro-8.09 (d, 1H, J = 5.4 Hz), 7.02 N 4 -methyl-4- (d, 1H, J = 2.4 Hz), 6.93 (d, pyrimidinamine 1H, J = 8.4 Hz), 6.84 (dd, 1H, J = 2.1 and 8.4 Hz), 3.75 (s, 3H), 3.71 (s, 3H); LCMS: purity: 87%, MS (m / e): 298 (M +) 418 2-chloro-N 4 - (3,4-ethylenedioxyphenyl) -5- LCMS: purity: 99%, EM fluoro-N 4 - (m / e): 354 (M +) (methoxycarbonylmethyl) -4- pyrimidinamine 419 N4- (3, 4-Dimethoxyifem) - 1 H NMR (DMSO-d 6): d 5-fluoro-N 2 - [3- (oxazole-9.29 (s, 1H), 9.21 (s, 1H), 5-ü) phenyl] -2.4- 8.33 (s, 1H), 8.07 (d, 1H, pyrimidinediamine J = 3.0 Hz), 8.04 (s, 1H), 7.61 ( bd, 1H), 7.39 (s, 1H), 7.29 + (bdd, 1H, J = 2.7 and 8.4 Hz), 7.25 (m, 3H), 6.76 (d, 1H, J = 8.7 Hz), 3.70 (s, 3H), 3.64 (s, 3H); LCMS: purity: 98%: purity: 98%, EM 420 N4- (3.4-1H NMR (DMSO-d6): d Ethylenedioxyphenyl) -5- 10.77 (s, 1H), 9.05 (s, 1H), fluoro -N2- (indol-6-yl) - 7.94 (d, 1H, J = 5.7 Hz), 7.70 N4- (s, 1H), 7.32 (d, 1H, J = 2.8 (methoxycarbonylmethyl) - Hz), 7.19 ( d, 1H, J = 1.5 Hz), + 2,4-pyrimidinediamine 7.17 (t, 1H, J = 3 Hz), 6.82 (m, 3H), 6.28 (d, 1H, J = 2.1 Hz), 4.60 (s) , 2H), 4.24 (s, 4H), 3.33 (s, 3H); LCMS: purity: 99 o. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 421 N4- (3, 4-dimethoxyphenyl) -1H NMR (DMSO-d6): d5-fluoro-N2- [2- (N- 11.66 (s, 1H), 9.27 (s, 1H), methylaminocarbonyl) - 9.22 (s, 1H), 8.41 (bd, 1H, indole-7-yl] -2.4- J = 4.8 Hz), 8.09 (d, 1H, J = 3.3 pyrimidinediamine Hz), 7.99 (d, 1H, J = 7.8 Hz), 7.33 (dd, 1H, J = 2.4 and 8.4 Hz), 7.28 (d, 1H, J = 2.7 Hz), 7.18 (d, 1H, J = 7.5 Hz), 7.03 (d, 1H, J = 2.1 Hz), 6.89 (m 422 N 4 - (3, 4-dimethoxyphenyl) -1 H NMR (DMSO-d 6): d 5-fluoro-N 2 - [4- (oxazole-9.36 (s, 1H), 9.24 (s, 1H), 5-yl) fenu] -2.4- 8.33 (s, 1H), 8.07 (d, 1H, p? Imdindiamine J = 3.9 Hz), 7.75 (d, 2H, J = 6.0 Hz), 7.50 ( d, 2H, J = 8.7 Hz), + + 7.75 (d, 2H, J = 8.7 Hz), 7.47 (s, 1H), 7.26 (m, 2H), 6.92 (d, 1H, J = 9.6 Hz), 3.76 (s, 3H), 3.69 (s, 3H); CLEM: purity 423 N4- (3,4-Dimethoxyphenyl) -1H NMR (DMSO-d6): d 5-fluoro-N2- [3- (oxazole-9.36 (s, 1H), 9.22 (s, 1H), 2-ü) phenyl] -2.4- 8.29 (s, 1H), 8.12 (s, 1H), p imidindiamine 8.08 (d, 1H, J = 3 Hz ), 7.81 (dd, 1H, J = 1.8 and 7.1 Hz), + + 7.49 (d, 1H), J = 6.9 Hz), 7.31 (m, 4H), 6.79 (d, 1H, J = 8.7 Hz), 3 .71 (s, 3H), 3.67 (s, 3H); LCMS: purity: 98%, MS (m / e): 40 424 N 4 - (3,4-Dimethoxyphenyl) -1 H NMR (DMSO-d 6): d 5-fluoro-N 2 - [4- (oxazole-9.50 (s) , 1H), 9.28 (s, 1H), 2-yl) phenyl] -2.4- 8.09 (syd, 2H, J = 4.5 Hz), pyrimidinediamine 7.76 (m, 4H), 7.28 (m, 3H), + 6.93 (d, 1H, J = 8.4 Hz), 3.76 (s, 3H), 3.70 (s, 3H); LCMS: purity: 89% (m / e): 408 (M +). 425 N2- (3-Chloro-4-1H NMR (DMSO-d6): d-methoxyphenyl) -N4- (3.4-9.17 (s, 1H), 9.08 (s, 1H), dimethoxyphenyl) -5-fluoro- 8.02 (d, 1H, J = 3.9 Hz), 7.84 2,4-pú ± midindiamine (s, 1H, J = 2.7 Hz), 7.41 (dd, + 1H, J = 3.0 and 9.3 Hz), 7.27 + + ( dd, lH, J = 2.4 and 8.7 Hz) 7.21 (d, 1H, J = 2.4 Hz), 6.97 9d, 1H, J = 8.7 Hz), 6.88 (d, 1H, J = 8.7 Hz, 3.77 (s, 3H ), or Compound Name Physical Data Triptase Triptase Triptase f syk or LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 426 N2- [3- (4-1H NMR (DMSO-d6): d Acetylpiperazine) phenyl] - 9.13 (s, 1H), 8.99 (s, 1H), N4- (3.4- 8.02 (d, 1H, J = 4.2 Hz), 7.22 ethylenedioxyphenyl) -5- (m, 4H), 7.03 (m, 1H), 6.77 fluoro-2,4- (d, 1H, J = 8.7 Hz), 6.50 (bd, + + pyrirm ^ indiamine 1H, J = 7.2 Hz), 4.21 (bs, 4H), 3.02 (bm, 2H), 2.95 (bm, 2H), 2.02 (s, 3H); LCMS: purity: 97%, MS (m / e): 465 (MH +). 427 N2- [4- (4-1H NMR (DMSO-d6): d Acetypiperazin) phenyl] -9.07 (s, 1H), 8.92 (s, 1H), N4- (3.4-7.98 (d, 1H, J = 3.9 Hz), 7.48 ethylenedioxyphenyl) -5- (d, J = 8.7 Hz), 7.33 (d, 1H, fluoro-2,4- J = 2.4 Hz), 7.18 (dd, 1H, + + - pyrimidinediamine J = 2.1 and 8.7 Hz), 6.83 (d, 1H, J = 9.3 Hz), 6.73 (d, 1H, J = 1H, J = 8.7 Hz), 4.23 (bs, 4H), 3.56 (bs, 4H), 3.03 (t, 2H, J = 5 428 N2- [3- (4-1H NMR (DMSO-d6): d Acetylpiperazine) phenyl] - 9.23 (s, 1H), 9.07 (s, 1H), + + N4- ( 3, 5-dimethoxyphenyl) - 8.09 (d, 1H, J = 3 Hz), 7.26 5-fluoro-2,4- (s, 1H), 7.15 (d, 1H, J = Hz), pyrimidinediamine 7.07 (t, 1H, J = 8.4 Hz), 6.97 (d, 2H, J = 2.4 Hz), 6.50 (bd, 1H, J = 7.5 Hz), 6.18 (d, 1H, J = 2.1 Hz), 5.74 (s, 1H) , 3.49 (m, 4H), 3.32 (s, 6H), 2.96 (429 N2- [3- (4-1H NMR (DMSO-d6): d acetylpiperazm) phenyl] - 9.17 (bs, 1H), 8.99 (s) , 1H), N4- (3,4-dimethoxyphenyl) -8.02 (d, 1H, J = 3.9 Hz), 7.27 5-fluoro-2,4- (m, 2H), 7.01 (bd, 1H, J = 8.4 pyrimidinediamine Hz), 7.00 (t, 1H, J = 8.1 Hz), + 6.86 (d, 1H, J = 8.4 Hz), 6.48 (bd, 1H, J = 9.9 Hz), 6.13 (bs, 1H), 3.72 (s, 3H), 3.62 (s, 3H), 3.46 (, 4H), 2.96 (m, 430 N2- [4- (4-1H NMR (DMSO-d6) : d acetylpi? erazin) phenyl] - 9.11 (s, 1H), 8.88 (s, 1H), N4- (3, 4-dimethoxyphenyl) - 7.98 (d, 1H, J = 3.9 Hz), 7.46 5-fluoro- 2.4- (d, 2H, J = 9.3 Hz), 7.27 (m, pyrimidiadiamine 2H), 6.87 (d, 1H, J = 8.4 Hz), 6.80 (d, 2H, J = 9 Hz), 3.74 (s) , 3H), 3.65 (s, 3H), 3.56 (m, 4H), 3.02 (m, 2H), 2.96 (m, 2H), 2.03 (s, 3H); CLEM: purity o. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 431 N2- [3- (4-1H NMR (DMSO-d6): d Acetylpiperazine) phenyl] -5- 9.62 (s, 1H), 9.19 (s, 1H), fluoro-N4- (3.4- 8.14 ( m, 1H), 7.62 (dd, 1H, (tetrafluoroethylenedioxife J = 2.7 and 9.6 Hz), 7.39 (d, 1H, nil) -2.4- 1 = 9 Hz), 7.23 (d, 1H, J = 8 + + - pyrirm ^ mcHamina Hz), 7.16 (s, 1H), 7.07 (t, 1H, J = 2.6 Hz), 6.55 (d, 1H, J = 2.6 Hz), 6.12 (s, 1H), 3.54 (bs, 4H), 2.02 (s, 3H); CLEM; 432 N2- [4- (4-1H NMR (DMSO-d6): d Acetylpiperazine) phenyl] -5- 9.57 (s, 1H), 9.11 (s, 1H), fluoro-N4- (3.4- 8.15 ( bd, 1H), 8.10 (d, 1H, (tetrafluoroethylenedioxife J = 3.3 Hz), 7.57 (bdd, 1H, nil) -2.4- J = 9.6 Hz), 7.45 (d, 2H, J = 8.7 + pyrimidinediamine Hz ), 7.37 (d, 1H, J = 9 Hz), 6.87 (d, 2H, J = 9.3 Hz), 6.69 (d, 1H, J = 8.7 Hz), 6.47 (d, 1H, J = 8.7 Hz), 3.52 (m, 4H), 2.99 433 N4- (3, 4-dimethoxyphenyl) -1H NMR (DMSO-d6): d N2- (3,5-dimethylphenyl) -5-9.05 (s, 1H), 7.89 (d , 1H, fluoro-N4-methyl-2,4- J = 6.0 Hz), 7.31 (s, 2H), 6.93 pyrimidinediamine (d, 1H, J = 2.7 Hz), 6.90 (s, 1H), 6.81 (dd, 1H, J = 2.4 and + 8.1 Hz), 6.50 (s, 1H), 3.75 (s, 3H), 3.71 (s, 1H), 3.42 (s, 3H), 2.18 (s, 6H), CLEM: purity: 95%, MS (m / e): 383 (MH +). 434 N2- (3,5-Dimethoxyphenyl) -N4- (3,4-dimethoxyphenyl) -MSC: purity: 96%, MS + 5-fluoro-N4 -methyl-2,4- (me): 415 (MH +). pirj ^ dmdiamina + or. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 436 N 4 - (3,4-Dimethoxyphenyl) -1 H NMR (DMSO-d 6): d 5-fluoro-N 2 - (indol-6-yl) - 10.85 (s, 1 H), 9.07 (s, 1 H), N 4 - methyl-2,4- 8.03 (s, 1H), 7.87 (d, 1H, pyrimidiamine J = 8.4 Hz), 7.34 (d, 1H, J = 8.7 Hz), 7.16 (m, 2H), 6.93 (, + 2H) ), 6.90 (s, 1H), 6.80 (, 1H), 6.28 (s, 1H), 3.75 (s, 3H), 3.73 (s, 3H), 3.44 (s, 3H); LCMS: purity: 94%, MS (m / e): 3 437 N2- [4- (4-Acetylpiperazine) phenyl] -MSCM: purity: 80%, N4- EM (3,5-dimethoxyphenyl) - (m / e): 467 (MH +) 5-fluoro-2,4-pyrimid diamine 438 N 4 - (3,4-dimethoxyphenyl) -1 H NMR (DMSO-d 6): d 5-fluoro-N 4 -methyl-N 2 - 9.42 (s) , 1H), 8.40 (s, 1H), [3- (oxazol-5-yl) phenyl] - 8.28 (bs, 1H), 7.93 (d, 1H, 2,4-pyrimid diamine J = 8.7 Hz), 7.58 (bd, 1H, J = 6.8 Hz), 7.55 (s, 1H), 7.27 + + (m, 2H), 6.96 (d, 1H, J = 2.4 Hz), 6.92 (m, 1H), 6.81 (dd, 1H, J = 2.1 and 8.4 Hz), 3.75 (s, 3H), 3.75 2 (s, 3H), 3.47 (s, 439 N4- (3,4-dimethoxyphenyl) -1H NMR (DMSO-d6): d 5 -fluoro-N4-methyl-N2- 9.50 (s, 1H), 8.62 (d, 1H, [3- (oxazol-2-yl) fenu] - J = 3.6 Hz), 8.17 (s, lH), 7.94 ( d, 1H, J = 6.0 Hz), 7.70 (dd, 1H, J = 2.4 Hz), 7.33 (m, 2H), 6.97 (d, 1H, J = 2.4 Hz), 6.92 (d, 1H, J = 8.4 Hz), 6.82 (dd, 1H, J = 2.4 and 8.7 Hz), 3.76 (s, 3H), 3.73 (s, 3H), 3.48 440 N4- (3, 4-dimethoxyphenyl) - 1H NMR (DMSO-d6) : d 5-fluoro-N 4 -methyl-N 2 - 9.59 (s, 1H), 8.10 (s, 1H), [4- (oxazol-2-yl) phenyl] - 7.98 (m, 2H), 7.62 (d d, 1H, 2,4-pyrimidiamine J = 2.1 and 6.6 Hz), 7.27 (s, 1H), 6.96 (m, 2H), 6.92 (s, 1H), 6.81 (dd, 2.4 and 8.4 Hz), 6.61 (dd, 1H, J = 2.1 and 6.6 Hz), 5.67 (bs, 1H), 3.77 (s, 3H), 3.72 (s, 3H), 3.45 (s, 3H). 41 N2- (3,5-Dimethylphenyl) -N4- (3,4-LCMS: purity: 91%, MS etiiodioxyphenyl) -5- (m / e): 439 (MH +). + fluoro-N 4 - (methoxycarbonylmethyl) -2,4-pyridinediamine o. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 442 N2- (3,5-Dimethoxyphenyl) -1H NMR (DMSO-d6): d N4- (3.4- 9.14 (s, 1H), 7.97 (d, 1H, ethylenedioxyphenyl) -5- J = 5.7 Hz) , 6.84 (m, 5H), fluoro-N4-6.07 (m, 1H), 4.62 (s, 2H), + (methoxycarbonylmethyl) - 4.24 (s, 3H), 3.68 (bs, 4H), 443 N2- [3- (oxazole-5-7.57 (s, 1H), 7.27 (, 2H), + ü) phenyl] -2.4-6.83 (m, 3H), 4.63 (s, 2H), pyrin? Dindiamine 4.23 (s, 4H), 3.51 (s, 3H); LCMS: purity: 95%, MS (m e): 478 (MH +). 444 N 4 - (3,4- 1 H NMR (DMSO-d 6): d Ethylenedioxyphenyl) -5-9.49 (s, 1H), 8.24 (s, 1H), fluoro-N4- 8.17 (s, 1H), 8.00 (d , 1H, (methoxycarbonylmethyl) - J = 5.7 Hz), 7.76 (bd, 1H, N2- [3- (oxazole-2-J = 9.6 Hz), 7.51 (bd, 1H, + il) phenyl] -2.4 - J = 8.1 Hz) 7.34 (m, 2H), 6.86 pyripindinediamine (m, 1H), 6.83 (m, 1H), 4.64 (s, 2H), 4.24 (s, 4H), 3.54 (s, 3H); LCMS: purity: 91%, MS (m / e): 478. 445 N4- (3.4-1H NMR (DMSO-d6): d Ethylenedioxyphenyl) -5- 9.61 (s, 1H), 8.10 (s, 1H ), fluoro-N4- 8.05 (d, 1H, J = 8.1 Hz), 7.77 (methoxycarbonylmethyl) - (dd, 2H, J = 8.4 Hz), 7.70 (dd, N2- [4- (oxazole-2H, J = 8.4 Hz), 7.29 (s, 1H), il) fepyl] -2.4-6.85 (m, 3H), 4.64 (s, 2H), pyrimidinediamine 4.25 (s, 4H), 3.63 (s, 3H); LCMS: purity: 92%, MS (m / e): 478 (MH +). 446 N4- (3.4- 1 H NMR (DMSO-d6): d Ethylenedioxyphenyl) -5- 9.24 (s, 1H), 7.97 (d, 1H, fluoro-N4- J = 5.7 Hz), 7.94 (m, 1H ), (methoxycarbonylmethyl) - 7.22 (m, 2H), 7.08 (t, 1H), N2-p- (N- J = 7.8 Hz), 6.83 (im, 3H), methyamin) carbonyl- 6.49 (m, 1H) , 4.62 (s, 2H), + methyleneoxyphenyl] -2.4-4.39 (s, 2H), 4.24 (s, 4H), pyrimidinediamine 3.60 (s, 3H), 2.66 (4, 3H, J = 5.1 Hz) CLEM : purity: 97%, MS (498 (MH +). or. Compound Name Physical Data Triptase Triptase Triptase f_syk om LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 447 N 4 - (3,4-Dimethoxyphenyl) -1 H NMR (DMSO-d 6): d 5-fluoro-N 4 -methyl-N 2 - 9.24 (s, 1H), 7.94 (bs, 1H), [3- (N- 7.90 (d, 1H, J = 5.7 Hz), 7.46 methylamin) carbonylmethyl (t, 1H, J = 2.1 Hz), 7.27 (bd, enoxyphenyl) -2.4- 1H, J = 9 Hz), 7.10 (t, 1H, + pyrimidinediamine J = 5.1 Hz), 6.93 (m, 1H), 6.79 (dd, 1H, J = 2.7 and 8.7 Hz), 6.45 (dd, 1H, J = 1.8 and 8.1 Hz) 6.12 (m, 1H) , 4.38 (s, 2,448 N2- [4-chloro-3- (N-1 H NMR (DMSO-d6): d methylamino) carbonyl- 9.37 (s, 1H), 9.18 (s, 1H), phenyl] -N4 - (3.4- 8.21 (d, 1H, J = 4.5 Hz), 8.05 ethylenedioxyphenyl) -5- (d, 1H, J = 3.6 Hz), 7.72 (m, fluoro-2,4-2H), 7.22 ( , 2H), 7.20 (m, + pyrimidiamidene 3H), 6.80 (bdd, lH, J = 2.1 and Hz), 4.11 (bs, 4H), 2.71 (d, 3H, J = 4.5 Hz); LCMS: purity: 95%; MS (m / e): 430 (MH +). 449 N2- [4-Chloro-3- (N- 1 H NMR (DMSO-d 6): d methylamino) carbonyl- 8.20 (d, 1 H), 8.05 (d, 1 H, phenyl) -N 4 - (3,4-J) = 3.9 Hz), 7.75 (d, 1H, J = 2.7 dimethoxyphenyl) -5-fluoro-Hz), 7.66 (dd, 1H, J = 3.0 and 2,4-pyrimidinediamine 8.7 Hz), 7.32 (dd, 1H, J = 2.4 + and 9.0 Hz), 7.23 (s, 1H), 7.18 (, 1H), 6.88 (d, 1H, J = 8.7 Hz), 4.00 (s, 4H), 3.76 (s, 3H), 3.71 (s) , 3H), 2.69 (d, 450 N2- [4-chloro-3- (N-1H NMR (DMSO-d6): d methyamin) carbomphenyl) 8.15 (d, 1H, J = 4.2 Hz), 7.82 -N4- (3,5-dimethoxyphenyl) - (dd, 1H, J = 2.7 and 9.0 Hz), 5-fluoro-2,4- 7.61 (d, 1H, J = 2.7 Hz), 7.25 pyrimidinediamine (d, 1H, J = 9.0 Hz), 6.96 (t, 2H, J = 2.4 Hz), 6.26 (t, 1H, J = 2.1 Hz), 3.71 (s, 6H), 2.71 (d, 3H, 3.3 Hz); LCMS: purity: 87%, MS (m / e): 432 (M +). 51 N4- (3-Chloro-4-1H NMR (DMSO-d6): d methoxyfenu) -N2- [4- 8.16 (d, 1H, J = 3.9 Hz), 7.70 chloro-3- (N- (d, 1H, J = 2.7 Hz), 7.64 (m, methylamin) carbonyl-2H), 7.30 (d, 1H, J = 9.3 Hz), + phenyl] -5-fluoro-2,4-7.10 (d, 1H, J = 9 Hz), 3.87 (s, pyrimidindiamine 3H), 2.69 (s, 3H); LCMS: purity: 91%, MS (m / e): 536 (M +) o. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 452 N4- [3-Chloro-4-1H NMR (DMSO-d6): d (ethoxycarbonyl- 1.1-9.65 (bs, 2H), 8.26 (d, 1H), dimethylmethyleneoxy) phenyl] - J = 4.8 Hz) , 8.17 (s, 1H), 7.80- N2- [4-chloro-3- (N- 7.58 (, 4H), 7.27 (d, 1H), methylamino) carbonyl- J = 8.7 Hz), 6.89 (d, 1H , J = 9 + + phenyl] -5-fluoro-2,4-Hz), 4.20 (q, 2H, J = 6.9 Hz), pmmidindiamine 2.71 (d, 3H, J = 4.2 Hz), 1.54 (s, 6H ), 1.21 (t, 3H, J = 7.2 Hz); LCMS: purity: 91%, MS (m / 453 N2- [4-Chloro-3- (N-1 H NMR (DMSO-d6): d methyamin) carbonyl- 9.69 (s, 1H), 8.28 (d, 1H, fenu] -N4- (3,4- J = 4.5 Hz), 7.98 (d, 1H, J = 6.0 ethylenedioxyphenyl) -5- Hz), 7.83 (d, 1H, J = 2.4 Hz), + fluoro-N4- methyl-4- 7.66 (dd, 1H, J = 2.7 and 8.7 pyrimidinediamine Hz), 7.29 (d, 1H, J = 9 Hz), 6.84 (m, 2H), 6.76 (dd, 1H, 2.7 and 8.7 Hz) 4.24 (s, 4H), 3.38 (s, 1H), 2.72 (d, 3H, J = 454 N2- [4-Chloro-3- (N-1 H NMR (DMSO-d6): d methyamin) carbonylphenyl] 9.50 (s , 1H), 8.26 (d, 1H, -N4- (3,4-dimethoxyphenyl) - J = 4.5 Hz), 7.93 (d, 1H, 6.0 5-fluoro-N4-methyl-4-Hz), 7.87 (d , 1H, J = 2.7 Hz), pm idindiamine 7.68 (dd, 1H, J = 2.4 and 5.7 Hz), 7.26 (d, 1H, J = 8.7 Hz), 6.93 (m, 2H), 6.80 (dd, 1H, J = 2.4 and 8.4 Hz), 3.76 (s, 3H), 3.76 (s, 3H), 3.72 (s, 3H), 1H NMR (DMSO-d6): d 10.71 (s, 1H), 9.87 (s, 1H ), N2- [4-Chloro-3- (N- 8.26 (d, 1H, J = 4.2 Hz), 8.16 methyamin) carboml- (d, 1H, J = 4.2 Hz), 7.63 (m, phenyl] -N4 - (2,2-dimethyl-3H), 7.25 (m, 2H), 7.17 (d, 455 oxo-4H-1H, J = 2.1 Hz), 6.90 ( d, 1H, + + benz [1,4] oxazin-6-yl) -5- J = 8.7 Hz), 2.71 (d, 3H, J = fluoro-2.4-4.5 Hz), 1.40 (s, 6H) ); pyrimidinediamine LCMS: purity: 97%, MS (m / e): 471 (M +). 1 H NMR (DMSO-d 6): d 10.74 (s, 1 H), 10.34 (s, 1 H), N 2 - [3-Chloro-4- (N-10.09 (s, 1 H), 8.24 (d, 1 H, J = methyamin) carbonyl- 4.8 Hz), 8.15 (d, 1H, J = 4.5 phenyl] -N4- (2,2-dimethyl-3 Hz), 7.83 (d, 1H, J = 1.5 Hz), 456 oxo-4H - 7.44 (dd, 1H, J = 1.8 and 8.4 + + + benz [1,4] oxazin-6-yl) -5-Hz), 7.23 (m, 2H), 6.93 (d, fluoro-2,4-) 1H, J = 8.4 Hz), 2.71 (d, 3H, pñipr? Dindiamine J = 4.2 Hz), 1.40 (s, 6H); LCM or. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 8.02 (d, 1H, J = 8.4 Hz), 7.87 N2- (2,6-dimethoxypyrid- (d, 1H, J = 6.4 Hz), 7.76 (s, 3-yl) -N4- (3.5-1H), 6.41 (m, 3H) , 6.32 (d, 457 dimethoxyphenyl) -5-fluoro-1H, J = J = 8.4 Hz), 3.89 (s, + + N4-methyl-2,4- 3H), 3.82 (s, 3H), 3.71 (s) , pyrimidindiamine 3H), 3.34 (s, 3H); LCMS: purity: 95%, MS (m e): 416 (MH +). 1 H NMR (DMSO-d 6); d 8.02 (d, 1H, J = 8.4 Hz), 7.82 (d, 1H, J = 6.6 Hz), 7.68 (s, N2- (2,6-dimethoxypyrid-1H), 6.79 (m, 2H), 6.72 (d, dd, 3-yl) -N4- (3,4- 1 H, J = 2.1 and 8.1 Hz), 6.30 458 ethylenedioxyphenyl) -5- (d, 1H, J = 8.1 Hz), 4.23 (s, fluoro-N4- methyl-2,4- 4H), 3.89 (s, 3H), 3.81 (s, pyrirnid diamine 3H), 3.28 (s, 3H); LCMS: purity: 97%, MS (m / e): 414 (MH +). 1 H NMR (DMSO-d 6): d 9.12 (s, 1 H), 7.97 (d, 1 H, J = 5.1 Hz), 7.89 (s, 1 H), 7.82 N 4 - (3,5-Dimethoxyphenyl) - (d, 1 H , J = 7.8 Hz), 6.95 (s, N2- (2,6-dimethoxypyrid-459 1H), 6.28 (d, 1H, J = 7.8 Hz), 3-yl) -5-fluoro-2,4- + 6.15 (s, 1H), 3.84 (s, 3H), pyrimidinediamine 3.83 (s, 3H), 23.64 (s, 6H); LCMS: purity: 85%, MS (m / e): 402 (MH +). N2- (2,6-Dimethoxypyrid-3-yl) -N4- (3,4-CLEM: purity: 93%, ilenedioxyphenyl) -5- EM 460 et + (m / e): 400 (MH +). fluoro-2,4-pyrimidinediamine 1 H NMR (DMSO-d 6): d N 4 - (3,4-7.72 (d, 1 H, J = 5.1 Hz), 6.79 Ethylenedioxyphenyl) -5- (d, 1 H, J = 9.0 Hz ), 6.73 (bs, 61 fluoro-N2-methyl-N4-1H), 6.66 (bd, 1H), 2.74 (d, methyl-2,4- 3H, J = 4.5 Hz); LCMS: pyrimidmdiamiaa purity: 93%, MS (m / e): 291 (MH +). 1 H NMR (DMSO-d 6): d 7.78 (d, 1 H, J = 6.0 Hz), 6.80 N 2 -Dimethyl-N 4 - (3,4- (d, 1 H, J = 8.4 Hz), 6.75 (d, ethylenedioxyphenyl) -5- 1H, J = 2.7 Hz), 6.66 (dd, 1H, 62 fluoro-N4-methyl-2,4- J = 1.8 and 8.4 Hz), 4.22 (s, pyrimidindiamine 4H), 3.31 (s, 3H) 3.30 (s, 3H); LCMS: purity: 95%; MS (m / e): 305 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.45 (s, 1H), 9.24 (s, 1H), N2- [3 -Cloro-4- (N- 8.11 (m, 2H), 7.89 (d, lH, J = methyamin) carbonyl- 2.1 Hz), 7.54 (dd, 2.1 and 8.7 phenyl] -N4- (3.4-463 Hz) ), 7.20 (m, 3H), 6.82 (d, ethylenedioxyphenyl) -5- 1H, J = 8.4 Hz), 4.22 (bs, fluoro-2,4- 4H), 2.71 (d, 3H, J = 4.5 Hz); pyrimidinediamine LCMS: purity: 99%, MS (m / e): 430 (MH +). 1 H NMR (DEMO-d 6): d 10.34 (s, 1H), 10.10 (s, 1H), 8.25 (d, 1H, J = 4.5 Hz), 8.18 N2- [3-Chloro-4- (N- (d , 1H, J = 4.8 Hz), 7.81 (s, methylamin) carbonylfeml] 1H), 7.41 (d, 1H, J = 8.1 Hz), 464 -N4- (3,4-dimethoxyphenyl) - 7.27 (d, 1H, J = 8.4 Hz), 7.18 5-fluoro-2,4- (m, 2H), 6.95 (d, 1H, J = 8.7 pyrimidirtediamine Hz), 3.75 (s, 3H), 3.68 (s, 3H), 2.71 ( d, 3H); LCMS: purity N2- [3-Chloro-4- (N-methylamino) carbonyl-LCMS: purity: 100%, EM 465 phenyl] -N4- (3.5- + (m / e): 432 (MH +). dimethoxyphenyl) -5-fluoro-2,4-? irimidindiamine N4- (3-Chloro-4-methoxyphenyl) -N2- [3-chloro-4- (N-CLEM: purity: 100%, EM 466 + methyl) carbonyl - (m / e): 436 (MH +). + phenyl] -5-fluoro-2,4-pyrirnidmdiamine N4- [3-Chloro-4- (ethoxycarbonyl-1,1-dimethylmethyleneoxy) phenyl] -MSCM: purity: 95%, EM 467 N2- [3-chloro- 4- (N- + (m / e): 536 (MH +). + + Methylamino) carbonyl-phenyl] -5-fluoro-2,4-pyrimidinediamine N 2 - [3-Chloro-4- (N-methylamino) carbonyl - LCMS: purity: 100%, EM 468 phenyl] -5-fluoro-N 4 - (3- + (m / e): 388 (MH +). + Hydroxyphenyl) -2,4-pyrimidindiainine No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 7.70 (d, 1H, J = 5.7 Hz), 6.79 N4- (3,4- (d, 1H, J = 8.7 Hz), 6.74 (d, Ethylenedioxyphenyl) -5- 1H, J = 2.4 Hz), 6.66 (dd, 1H, 469 fluoro-N2- (2- J = 2.4 and 8.4 Hz), 6.50 (t, 1H, bidroxietü) -N4-methyl- J = 5.1 Hz), 4.61 (t, 1H, J = 2,4-? Irimidindiamine 5.4 Hz), 4.22 (s, 4H) , 3.47 (q, 2H, J = 6.3 Hz), 3.29 (t, 2H, J = 5.4 Hz), 3.25 (s, 3H) 1H NMR (CDC13): d 7.87 (d, 1H, J = 7.8 Hz), 7.25 (, 2-Chloro-N4- [3-chloro-4-1H), 6.95 (m, 2H), 4.25 (q, (ethoxycarboni) l-1,1- 2 H, J = 4.8 Hz), 3.46 (s, 3H), 470 dimethylmethyleneoxy) phenyl] -1.65 (s, 6H), 1.29 (t, 3H, J = 5-fluoro-N4-methyl- 4- 4.8 Hz); LCMS: purity: pyrirm ^ inamine 95%, MS (m e): 404 (MH +, C137). 1 H NMR (DMSO-d 6): d 7.70 (d, 1H, J = 5.7 Hz), 6.77 (d, 1H, J = 8.7 Hz), 6.37 (d, N4- (3.4-1H, J = 2.4 Hz ), 6.68 (dd, 1H, ethylenedioxyphenyl) -5- J = 2.4 and 8.7 Hz), 6.44 (d, 1H, 471 fluoro-N2-isopropyl-N4- J = 8.1 Hz), 4.22 (s, 4H), 3.90 methyl-2,4- (sept, 1H, J = 7.5 Hz), 3.27 p ± nidindiamine (s, 3H), 1.12 (d, 6H, J = 6.6 Hz); LCMS: purity: 93%, MS 1 H NMR (DMSO-d 6): d 10.39 (s, 1H), 9.52 (s, 1H), 8.20 (d, 1H, J = 5.7 Hz), 7.77 N2- (2.6 -Dimethoxypyrid- (m, 1H), 7.08 (m, 1H), 6.59 3-yl) -5-fluoro-N4- (3-472 (m, 1H), 6.45 (d, 1H, J = 8.4 + Hdroxyphenyl) -2.4 Hz), 6.37 (d, 1H, J = 8.1 Hz), pyrimidmdiamine 3.88 (s, 3H), 3.86 (s, 3H); LCMS: purity: 89%, MS (m / e): 358 (MH +). 1 H NMR (DMSO-d 6): d 9.71 (s, 1 H), 8.16 (d, 1 H, J = N 2 - [3-Chloro-4- (N- 4.5 Hz), 8.00 (d, 1 H, J = 5.7 methyamin ) carbonü- Hz), 7.95 (d, 1H, J = 1.8 Hz) phenyl] -N4- (3,4-7.53 (dd, 1H, J = 2.1 and 8.4 473 + etxendioxyphenyl) -5- Hz), 7.29 ( d, 1H, J = 8.4 Hz), fluoro-N4-methyl-2,4-6.85 (m, 2H), 6.77 (dd, 1H, p? inñdindiamine J = 2.1 and 8.4 Hz), 4.24 (s, 4H) , 3.40 (s, 3H), 2.71 (d, 3H, No. Compound Name Physical Data Triptase Triptase Tftasa f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR 0JMSO-d6): d 9.86 (bs, lH), 8.18 (d, lH, J = N2- [3-Chloro-4- (N- 4.5 Hz), 8.03 (dd, 1H, J = 1.2 methylamin) carbonyl- and 6.3 Hz), 7.94 (d, 1H, J = 1.8 phenyl] -N4- (3.4-474 Hz), 7.52 (dd, 1H, J = 2.1 and dimethoxyphenyl) -5-fluoro- 8.4 Hz), 7.30 (d, 1H, J = 8.4 N4-methyl-2,4-Hz), 6.99 (d, 1H, J = 2.4 Hz), pyriridinediamine 6.93 (d, 1H, J = 8.4 Hz), 6.86 (dd, lH, J = 2.4 and 8. 1 H NMR (DMSO-d6): d 10.11 (s, 1H), 9.83 (s, 1H), N4- [4-Chloro-3- (N- 8.30 (d, 1H, J = 4.5 Hz), 8.24 met amin) carbonyl- (d, 1H, J = 4.5 Hz), 8.00 (dd, 475 phenyl) -N2- (3.5-lH, J = 2.7 and 8.7 Hz), 7.63 (d, + dimethoxyphenyl) -5- fluoro- 1H, J = 2.4 Hz), 7.36 (d, 1H, 2,4-? irimidindiamine J = 8.7 Hz), 6.78 (d, 2H, J = 2.1 Hz), 6.20 (t, 1H, J = 2.1 Hz ), 3.67 (s, 6H), 2.73 (d, 1H NMR (DMSO-d6): d 9.91 (s, 1H), 9.52 (s, 1H), 8.29 (d, 1H, J = 4.8 Hz), 8.19 N4 - [4-Chloro-3- (N- (d, 1H, J = 4.2 Hz), 8.00 methylamin) carbonyl- (bdd, 1H, J = 8.7 Hz), 7.62 476 phenyl] -N2- (3.5- (d, 1H, J = 2.1 Hz), 7.38 (d, + dimethylphenyl) -5-fluoro-1H, J = 9.0 Hz), 7.17 (s, 2H), 2,4-? irinridmdi-tmina 6.63 (s, 1H), 2.72 (d, 3H, J = 4.8 Hz), 2.19 (s, 6H); LCMS: purity: 1H NMR (DMSO-d6): d 9.55 (s, 1H), 9.32 (s, 1H), N4- [4-Chloro-3- (N- 8.31 (bd, 1H), 8.15 (bs, 1H), methylamino) carbonyl- 7.99 (m, 2H), 7.79 (m, 1H), phenyl] -5-fluoro-N2- [3- 7.39 (d, 1H, J = 9 Hz), 7.29 477 + (N -methylamin) carbonyl- (m, 2H), 7.14 (m, 1H), 6.49 methyleneoxyphenyl] -2,4- (bd, 1H, J = 7.8 Hz), 4.36 (s, pyrimidinediamine 2H), 2.72 (s, 3H) ), 2.64 (s, 3H); LCMS: purity: 99%, MS (m / e): 4 1 H NMR (DMSO-d 6): d 9.69 (s, 1 H), 8.34 (d, 1 H, J = N 2 - [3-Chloro-4- (N - 4.5 Hz), 8.22 (d, 1H, J = 3.6 methylamin) carbonyl- Hz), 8.17 (d, 1H, J = 4.5 Hz), phenyl] -N4- [4-chloro-3- (N- 478 7.95 (dd, 1H, J = 2.7 and 8.7 methyamin) carbonyl-Hz), 7.81 (d, 1H, J = 2.1 Hz), phenyl] -5-fluoro-2,4-7.71 (d, 1H, J = 2.7 Hz ), 7.56 pyrimidinediamy (dd, 1H, J = 2.1 and 8.4 Hz), 7.43 (d, lH, J = 9.0 Hz), 7.3 No. Compound Name Physical Data Tftase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC , CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 11.98 (s, 1H), 10.28 (s, 1H), 10.05 (s, 1H), 8.35 (d, 1H, J = N4- [4-Chloro-3- (N- 4.2 Hz), 8.21 (d, 1H, J = 4.8 methyamin) carbonylphenyl] Hz), 7.86 (bd, 1H, J = 8.7 479 -N2- (indole- 6-yl) -2.4-Hz), 7.77 (d, 1H, J = 2.7 Hz), pyrid id diamine 7.54 (s, 1H), 7.47 (d, 1H, J = 8.4 Hz), 7.35 (d, 1H, J = 8.7 Hz), 7.30 (m, 1H), 7.05 (dd, 1 N4- (3,4-ethylenedioxyphenyl) -5- CLEM: purity: 97%, EM 480 fluoro-2-methoxy-N4- ( m / e): 2 92 (M +). methyl-4-pyridineamine 1H NMR (DMSO-d6): d 9.85 (bs, 1H), 9.50 (bs, 1H), N4- [3-Chloro-4- (N- 8.22 (m, 2H), 7.89 ( m, 2H), methyamin) carbonylphenyl] 7.33 (d, 1H, J = 9.0 Hz), 6.85 481 -N2- (3,5-dimethoxyphenyl) - (d, 2H, J = 1.5 Hz), 6.13 (d, + + 5-fluoro-2,4- 1 H, J = 1.8 Hz), 3.66 (s, 1 H), pM-pindindiamine 2.74 (d, 3 H, J = 4.5 Hz); LCMS: purity: 98%, MS (m / e): 432 (M +). 1 H NMR (DMSO-d 6): d 10.01 (s, 1 H), 9.65 (s, 1 H), N 4 - [3-Chloro-4- (N- 8.24 (d, 1 H, J = 4.5 Hz), 7.85 methylamin) carbonylphenyl] (bs, 1H), 7.35 (d, 1H, J = 8.7 482 -N2- (3,5-dimethylphenyl) -5-Hz), 7.16 (s, 2H), 6.94 (s, + + fluoro-2) , 4- 2H), 6.65 (s, 1H), 2.74 (d, pyrin? D diamine 3H, J = 4.8 Hz), 2.29 (s, 3H), 2.20 (s, 3H); LCMS: purity: 98%, MS (m / e): 400 (M +). 1 H NMR (DMSO-d 6): d 9.82 (bs, 1H), 9.56 (bs, 1H), N 4 - [3-Chloro-4- (N- 8.22 (, 2H), 7.98 (bd, 1H), methylamino) carbonylphenyl] 7.91 (d, 1H, J = 1.5 Hz), 7.82 -5-fluoro-N2- [3- (N- (bd, 1H, J = 8.7 Hz), 7.37 (d, 483 methylamin) carbommethyl 1H, J = 8.7 Hz), 7.22 (m, enoxyphenyl) -2.4- 3H), 6.56 (m, 1H), 4.38 (s, pyrimidinediamine 2H), 2.74 (d, 3H, J = 4.5 Hz), 2.64 (d, 3H, J = 4.8 Hz); LCMS: pu 1 H NMR (DMSO-d 6): d N 2 - [4-Chloro-3- (N- 9.69 (s, 1 H), 9.60 (s, 1 H), methylamino) carboml-8.25 (m, 3 H), 7.85 (m, 3H), phenyl] -N4- [3-chloro-4- (N- 484 7.36 (m, 3H), 2.75 (d, 3H, J methylamino) carbonyl- 4.8 Hz), 2.70 (d, 3H, J = 4.5 phenyl] -5-fluoro-2,4-Hz); LCMS: purity: 86%, pyrimidimediamine MS (m e): 463 (M +).

No. Name of Compound Physical Data Tftase Tftasa Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.99 (s, 1H) , 10.10 (s, 1H), 9.80 (bs, 1H), 8.25 (d, 1H, J = N4- [3-Chloro-4- (N- 4.5 Hz), 8.20 (d, 1H, J = 4.2 methyamin) carbonyl- Hz), 7.93 (d, 1H, J = 1.8 Hz), 485 fenu] -5-fluoro-N2- + + 7.83 (bd, 1H, J = 9.6 Hz), (indole-6-yl) -2 , 4-7.58 (s, 1H), 7.47 (m, 2H), pyrimidinediamine 7.30 (, 2H), 7.12 (bd, 1H, J = 8.1 Hz), 6.38 (s, 1H); LCMS: p 1 H NMR (CD30D): d 8.16 N 4 - (2-Amino? Irid-6-yl) - (d, 1 H, J = 3.6 Hz), 7.46 (, 486 2-chloro-5-fluoro-4-) 2H), 6.32 (dd, 1H, J = 3.9 and pyrimidiamine 5.1 Hz); LCMS: purity: 92%, MS (m / e): 240 (M +). 1 H NMR (CD30D): d 7.43 (d, 1H, J = 7.2 Hz), 6.83 (d, N4- (3.4-1H, J = 8.4 Hz), 6.78 (d, 1H, Ethylenedioxyphenyl) -5- J = 2.4 Hz), 6.72 (dd, 1H, J = 487 fluoro-N4-methyl-2,4- 2.7 and 8.4 Hz), 4.25 (s, 4H), pnedimidiamine 3.40 (s, 3H); LCMS: purity: 100%, MS (m / e): 278 (MH +). 1 H NMR (CD30D): d 7.93 2-Chloro-N4- (3.5- (d, 1H, J = 5.4 Hz), 6.46 (s, dimethoxyphenyl) -5-fluoro-488 3H,), 4.62 (s, 6H), 3.77 (s, + N4-methyl-4- 3H); LCMS: purity: 100%, pyrmidinamine MS (m e): 298 (MH +). 1 H NMR (CD30D): d 7.73 (m, 2H), 7.34 (dd, 1H, J = 1.2 N2- (2- and 8.1 Hz), 7.17 (s, 1H), 7.04 Ethoxycarbonylindol-7-yl) - (t , 2H, J = 7.8 Hz), 4.38 (q, 489 5-fluoro-N4- (2- 2H, J = 6.9 Hz), 3.69 (t, 2H, hydroxyethyl) -2.4- J = 5.1 Hz), 3.58 (t, 2H, J = pyrimidinediamine 6.6 Hz), 1.42 (t, 3H, J = 7.2 Hz); LCMS: purity: 98%, MS (m / e): 360 (MH +). 1 H NMR (CD30D): d 7.89 (d, 1H, J = 5.7 Hz), 7.57 (d, 2-Chloro-N4- (2.6-1H, J = 8.1 Hz), 6.37 (d, 1H, dimethoxypyrid- 5-yl) -5- 490 J = 8.7 Hz), 3.94 (s, 3 H), 3.91 fluoro-N 4 -methyl-4- (s, 3 H), 3.37 (s, 3 H); LCMS: pyridinamine purity: 97%, MS (m / e): 299 (MH +). 1 H NMR (CD30D): d 8.02 2-Chloro-N 4 - (3,5- (d, 1 H, J = 5.4 Hz), 7.43 (s, dichloro-4-methoxyphenyl-5 491 2 H), 3.91 (s, 3H), 3.47 (s, fluoro-N 4 -methyl-4H); LCMS: purity: 89%, pyrirmdomine MS (m / e): 366 (MH +).

No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3? T IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 7.76 (d, 1H, J = 4.7 Hz), 6.79 N2- Bis -2-hydroxyethyl) - (d, 1H, J = 6.3 Hz), 6.75 (d, N4- (3.4-1H, J = 2.4 Hz), 6.67 (dd, 1H, 492 ethylenedioxypheni) -5- J = 2.7 and 9.3 Hz), 4.71 (bs, fluoro-N4-methyl-2,4-2H), 4.22 (bs, 4H), 3.57 (bs, pyrimidindiamine 4H), 3.31 (bs, 4H), 3.28 (s, 3H ); LCMS: purity: 97%, MS (m / e): 416 (MH +). 1 H NMR (DMSO-d 6): d 9.58 (s, 1 H), 9.29 (s, 1 H), N 4 - (3,4-8.11 (d, 1 H, J = 3.6 Hz), 7.47 Ethylenedioxyphenyl) -5- (m , 2H), 7.42 (bdd, 1H), 7.27 fluoro-N2- [4- (N- (d, 1H, J = 2.1 Hz), 7.13 (dd, 493 + + methylamino) sulfonyl-3- lH, J = 2.1 and 8.4 Hz), 6.79 (d, methoxyphenyl) -2,4- 1 H, J = 8.7 Hz), 6.73 (m, pyrimidinediamine 1 H), 4.22 (s, 4 H), 3.68 (s, 3 H), 2.34 (d , 3H, J = 4.8 Hz); L 1 H NMR (DMSO-d 6): d 9.57 (s, 1 H), 9.33 (s, 1 H), N 4 - (3,4-dimethoxyphenyl) -8.11 (d, 1 H, J = 3.6 Hz), 7.51 5-fluoro -N2- [3- (d, 1H, J = 1.8 Hz), 7.45 (d, 494 methoxyphenyl-4- (N- 1H, J = 8.4 Hz), 7.34 (dd, 1H, + + methylamin) sulfonyl] - 2.4- J = 1.8 and 8.7 Hz), 7.24 (m, pyrimidinediamine 2H), 6.90 (d, 1H, J = 9.0 Hz), 6.72 (d, 1H, J = 4.8 Hz), 3.75 (s, 3H) , 3.67 (s, 3 H), 3.63 (1 H NMR (DMSO-d 6): d 9.64 (s, 1 H), 9.37 (s, 1 H), N 4 - (3,5-Dimethoxyphenyl) - 8.16 (bd, 1 H), 7.51 (m, 3H), 5-fluoro-N2- [3-6.97 (bs, 2H), 6.71 (bd, 1H), 495 methoxyphenyl-4- 6.24 (bs, 1H), 3.69 (s, 6H), ( methyamin) sulfonyl] - 3.31 (s, 3H), 2.34 (d, 3H, J = 2,4-pi? imidindiamine 4.8 Hz); LCMS: purity: 94%, MS (m / e): 464 (M +). 1 H NMR (DMSO-d 6): d 10.62 (s, 1H), 9.50 (s, 1H), N 4 - (2,2-Dimethyl-3-oxo- 9.43 (s, 1H), 8.12 (d, 1H, J = 4 H -benz [1,4] oxazin-6- 3.9 Hz), 7.46 (s, 1 H), 7.44 (s, il) -5-fluoro-N 2 - [3- 496 1 H), 7.26 (dd, 1 H, J = 2.4 and + + methoxyphenyl-4- 8.7 Hz), 7.14 (d, 1H, J = 2.4 (methylamin) sulfoml] - Hz), 6.90 (d, 1H, J = 8.4 Hz), 2,4-α-mindindiamine 6.70 (d, 1H, J = 5.4 Hz), 3.69 (s, 3H), 2.32 (d, 3H, J = No. Compound Name Physical Data Triptase Triptase Tftase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.88 (s, 1H), 9.72 (s, 1H), N4- (4 -Cloro-3- 8.26 (m, 2H), 8.18 (d, 1H, J = trifluoromethylphenyl) -5- 4.5 Hz), 7.65 (d, 1H, J = 8.7 fluoro-N2- [3 Hz], 7.51 ( d, 1H, J = 8.7 Hz), 497 methoxyphenyl-4- 7.44 (m, 2H), 6.74 (d, 1H, J = + + (methyamin) sulfonyl] - 8.4 Hz), 3.72 (s, 3H), 2.34 2,4-pyrimidinediamine (d, 3H, J = 5.1 Hz); LCMS: purity: 97%, MS (m / e): 506 (M +). 1 H NMR (DMSO-d 6): d 9.78 (s, 1 H), 9.72 (s, 1 H), N 4 - (3-Chloro-4- 8.25 (, 1 H), 8.15 (d, 1 H, J = trifluoromethoxyphenyl) -5 - 3.6 Hz), 7.84 (dd, 1H, J = 2.4 fluoro-N2- [4- (3- 498 and 9.0 Hz), 7.52 (m, 2H), 7.43 methoxyphenyl-N- + (m, 2H), 6.74 (m, 1H), 3.74 methylamin) sulfonu] -2.4- (s, 3H), 2.33 (d, 3H, J = 2.1 pyrimidinediamine Hz); LCMS: purity: 83%, MS (m / e): 522 (M +). 1 H NMR (DMSO-d 6): d 9.57 (s, 1 H), 9.38 (s, 1 H), 9.31 (s, 1 H), 8.13 (d, 1 H, J = 5-Fluoro-N 4 - (3- 3.9 Hz) , 7.51 (m, 1H), 7.47 hydroxyphenyl) -N2- [3- (m, 2H), 7.21 (d, 1H, J = 1.5 499 methoxyphenyl-4- (N-Hz), 7.08 (m, 2H), 6.70 (d, + + methylamin) sulfonyl] -2, 4-1H, J = 5.4 Hz), 6.51 (bdd, pyrinidinediamine 1H, J = 8.1 Hz), 3.31 (s, 3H), 2.30 (d, 3H, J = 2.4 Hz); LCMS: puri 1H NMR (DMSO-d6): d 7.66 (d, 1H, J = 5.4 Hz), 7.59 N4- (2,6-dimethoxypyrid- (d, 1H, J = 7.5 Hz), 6.54 (bd, 3 -yl) -N2, N4-dimethyl-5-1H), 6.35 (d, 1H, J = 8.4 Hz), 500 fluoro-2,4- 3.85 (s, 3H), 3.83 (s, 3H), pyrirnidinediamine 2.71 (d, 3H, J = 3.9 Hz); LCMS: purity: 92%, MS (m / e): 294 (M +). 1 H NMR (DMSO-d 6): d N 4 - (3,5-Dichloro-4- 7.86 (d, 1 H, J = 5.4 Hz), 7.42 methoxyphenyl) -N 2, N 4 - (s, 2 H), 3.80 (s, 3H), 3.38 (s, 501 dimethyl-5-fluoro-2,4-3H), 2.73 (d, 3H, J = 4.8 Hz); pà ± a? dmdiamina LCMS: purity: 98%, MS (m / e): 331 (M +).

No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 10.28 (s, lH), 8.42 (d, lH, J = 3.0 Hz), 7.71 (d, 1H, J = 1.8 2-Chloro-5-fluoro-N4- [4- Hz), 7.67 (d, 1H, J = 8.4 Hz ), (N-methyl) sulfonyl-3- 7.46 (dd, 1H, J = 1.5 and 8.4 502 methoxyphenyl) -2,4-Hz), 6.95 (d, 1H, J = 5.4 Hz), pyrimidinamine 3.87 (s, 3H), 2.38 (2.38 (d, 3H, J = 4.8 Hz), LCMS: purity: 80%, MS (m / e): 349 (M + 2). 1H NMR (DMSO-d6): d 9.34 (s) , 1H), 9.14 (s, 1H), 8.57 (d, 1H, J = 2.7 Hz), 8.08 N2- (3,5-Dimetoxifeml) - (d, 1H, J = 3.0 Hz), 7.98 (dd, 5 -fluoro-N4- [2- (2-503 1H, J = 2.7 and 8.7 Hz), 6.91 (d, + hydroxyethyleneoxy) pyrid-5- 2H, J = 1.8 Hz), 6.77 (d, 1H, ü] - 2,4-pyrimidinediamine J = 8.7 Hz), 6.03 (t, 1H, J = 3.6 Hz), 4.23 (t, 2H, J = 4.5 Hz), 3.69 (m, 2H), 3.65 (s, 1H NMR (DMSO -d6): d 9.30 (s, 1H), 9.06 (s, 1H), 8.54 (d, 1H, J = 2.4 Hz), 8.06 N2- (3,5-Dimethylphenyl) -5- (d, 1H, J = 3.6 Hz), 7.94 (dd, fluoro-N4- [2- (2-504 1H, J = 2.7 and 9.0 Hz), 7.20 (d, hydroxyethyleneoxy) pyrid-5- 2H, J = 0.9 Hz), 6.79 (d, 1H, il] -2,4-? Üimidmdiarnine J = 9.0 Hz), 6.50 (s, 1H), 4.8 (t, 1H, J = 5.7 Hz), 4.23 (t, 2H, J = 5.7 Hz), 3.70 (q, 2 1H NMR (DMSO-d6): d 9.35 (s, 1H), 9.17 (s, 1H), N2- (3-Chloro-4-8.49 (s, 1H), 8.07 (d, 1H, J = methoxyphenyl) -5-fluoro- 3.6 Hz), 7.98 (dd, 1H, J = 2.7 505 N4- [2- (2- and 9.0 Hz), 7.81 (s, 1H), 7.40 + hydroxyethyleneoxy) pyrid-5- (bd, 1H, J = 8.7 Hz), 6.98 (d, il] -2,4-? irimidindiamine 1H, J = 8.4 Hz), 6.80 (d, 1H, J = 8.7 Hz), 4.83 (t, 1H, J = 5.7 Hz), 4.24 (t, lH, J = 4.8 1 H NMR (DMSO-d 6): d 7.70 (d, 1H, J = 4.4 Hz), 7.68 (m, 2H), 7.66 (dd, 1H, J = 1.2 N2-Allyl-N4- (3.4 - and 7.8 Hz), 5.85 (m, 1H), 5.10 ethylenedioxyphenyl) -5- (dd, 1H, J = 1.5 and 16.8 Hz), 506 fluoro-N4-methyl-2,4- 5.00 (dd, 1H, J = 1.8 and 12.0 pj jmiidindiamine Hz), 4.22 (s, 4H), 3.83 (t, 2H, J = 4.5 Hz), 3.28 (s, 3H); LCMS: purity: 100%, MS (ra No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- (3.5 -Dimethoxyphenyl) -5-fluoro-N4- [4- (N-CLEM: purity: 80%, EM 507 methylamm) sulfonyl-3- + + (me): 464 (MH +) methoxyphenyl] -2,4-pyrir dindia ina 1 H NMR (DMSO-d 6): d 9.50 (s, 1 H), 9.22 (s, 1 H), 8.16 (s, 1 H), 8.13 (dd, 1 H, J = N 2 - (3,5-Dimetoxifem) - 0.9 and 6.6 Hz), 8.06 (d, 1H, J = 5-fluoro-N4- (3- 8.7 Hz), 7.55 (bdd, 1H, J = 508 + + methylpyrid-6-yl) -2.4- 5.7 Hz), 6.94 (d, 2H, J = 1.2 pij ± mdmdiamine Hz), 6.07 (t, 1H, J = 1.2 Hz), 3.68 (s, 3H), 3.66 (s, 3H), 2.49 (s, 6H); LCMS: purity: 9 1 H NMR (DMSO-d 6): d 9.46 (s, 1H), 9.14 (s, 1H), 3.17 (bs, 1H), 8.13 (d, 1H, J = N2- (3.5- Dimethylphenyl) -5- 3.3 Hz), 8.04 (d, 1H, J = 8.4 fluoro-N4- (3-methylpyrid-Hz), 7.55 (dd, 1H, J = 2.1 and 509 + + 6-ü) -2, 4- 8.4 Hz), 7.24 (s, 2H), 6.24 (s, pyrimidinediamine 1H), 3.33 (s, 3H), 3.32 (s, 3H), 2.18 (s, 3H);; LCMS: purity: 93%, MS (m / e): 324 (MH + N 4 - (5-Chloropyrid-2-yl) - N 2 - (3,5-dimethoxyphenyl) - LCMS: purity: 93%, MS 510 5- fluoro-2,4- (me): 376 (MH +). pyrimidinediamthine 1 H NMR (DMSO-d 6): d 9.39 (s, 1H), 9.30 (s, 1H), 9.22 (s, 1H), 8.29 (bs, 1H), 5-Fluoro-N4- (3- 8.14 (s, 1H), 8.11 (d, 1H, J = hydroxifeml) -N2- [3- 511 3.9 Hz), 7.90 (dd, 1H, J = 1.2 + (oxazol-2-yl) phenyl] -2.4- and 9.0 Hz), 7.50 (dd, 1H, J = pyrimidiamine 1.5 and 6.3 Hz), 7.33 (m, 3H), 7.09 (t, 1H, J = 2.1 Hz), 7.01 (t, 1H, J = 8.1 Hz), 6.45 9d 1H NMR (DMSO-d6): d 9.54 (s, 1H), 9.26 (s, 1H), 512 LCMS: pururity: 91%, MS (m / e): 406 (M +).

No. Name of Compound Physical Data Tftase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 9.53 (s, 1H ), 9.29 (s, 1H), 8.21 (s, 1H), 8.10 (d, 1H, J = N4- (3, 4-dimethoxyphenyl) - 3.9 Hz), 7.79 (dd, 1H, J = 1.2 5-fluoro -N2- [3- (1, 2.4- 513 and 8.4 Hz), 7.33 (m, 3H), 7.16 oxadiazol-3-yl) phenyl] - + (s, 1H), 6.94 (d, 1H, J = 8.7 2,4-pyridinephraramine Hz), 3.75 (s, 3H), 3.70 (s, 3H); LCMS: purity: 95%, MS (m / e): 407 (MH-). 1 H NMR (DMSO-d 6): d 1.6 (s, 1 H), 9.49 (s, 1 H), 9.40 (, N 4 - (2,2-Dimethyl-3-oxoes, 1 H), 8.15 (d, 1 H, J = 8.1 4H-benz [1,4] oxazin-6 Hz), 8.11 (d, 1H, J = 3.9 Hz), il) -5-fluoro-N2- [3- 514 7.85 (bd, 1H, J = 8.4 Hz), + (1, 2,4-oxadiazole-3-7.29 (m, 3H), 7.13 (d, 1H, J = il) phenyl] -2.4- 2.4 Hz), 6.91 (dd, 1H , J = 3.0 pMmidindiamine and 8.4 Hz), 5.73 (d, 1H, J = 3.6 Hz), 1.40 (s, 3H); CLEM 1 H NMR (DMSO-d 6): d 9.61 (s, 1 H), 9.27 (s, 1 H), 8.62 (s, 1 H), 8.38 (s, 1 H), N 4 - (3,4-Dimethoxyphenyl) - 8.17 ( d, 1H, J = 0.9 Hz), 8.12 5-fluoro-N2- [5- (d, 1H, J = 3.6 Hz), 8.04 (d, 515 methoxycarbonyl-3- + 1H, J = 1.5 Hz), 7.35 (m, (oxazol-2-yl) phenyl] -2,4- 2 H), 7.27 (m, 1 H), 6.76 (d, pyrimidinediazine 1 H, J = 7.8 Hz), 3.82 (s, 3 H), 3.70 (s) , 3H), 3.65 (s, 3H); LCMS: pur 1 H NMR (DMSO-d 6): d 9.64 (s, 1 H), 9.23 (s, 1 H), N 4 - (3.4- 8.61 (s, 1 H), 8.37 (s, 1 H), Ethylenedioxyphenyl) - 5- 8.19 (s, 1H), 8.12 (d, 1H, J = fluoro-N2- [5- 3.3 Hz), 8.05 (s, 1H), 7.38 516 methoxycarbonyl-3 - (m, 2H), 7.22 (dd) , 1H, J = 2.7 (oxazol-2-ü) feml] -2.4- and 8.7 Hz), 6.70 (d, 1H, J = 8.7 pirirr? Dmdia ina Hz), 5.74 (s, 1H), 4.15 ( s, 4H), 3.85 (s, 3H); LCMS: purit 1 H NMR (DMSO-d 6): d 10.51 (s, 1 H), 9.54 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo- 9.40 (s, 1 H), 8.63 (s, 1H), 4H-benz [1,4] oxazin-6-8.39 (s, 1H), 8.18 (s, 1H), il) -5-fluoro-N2- [5- 8.14 (d, 1H, J = 3.9 Hz), 8.04 517 methoxycarbonyl-3 - (s, 1H), 7.44 (dd, 1H, J = 2.1 (oxazol-2-yl) phenyl] -2.4- and 8.7 Hz), 7.37 (s, 1H), 6.77 pyrimidinediamine (d, 1H, J = 8.4 Hz), 3.84 (s, 3H), 1.38 (s, 6H); CLEM: puri No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.64 (s, 1H), 9.25 (s, 1H), 8.62 (s, 1H), 8.43 (s, 1H), 5-Fluoro-N4- (3- 8.19 (s, 1H), 8.15 (d, 1H, J = hydroxyphene) -N2- [5- 3.9 Hz), 8.05 (s, 1H), 7.38 (s, 518 methoxycarbonyl-3H), 7.36 (s, 2H), 7.13 (s, (oxazol-2-yl) phenyl] - 2.4-1H), 6.98 (t, 1H, J = 8.7 Hz), pyrimidinediamine 6.42 (dd, 1H, J = 2.4 and 6.6 Hz), 3.83 (s, 3H); LCMS: purit 1 H NMR (DMSO-d 6): d 9.75 (s, 1 H), 9.23 (s, 1 H), 8.59 (s, 1 H), 8.22 (t, 2 H, J = N 4 - (3.4- 0.9 Hz ), 8.14 (d, 1H, J = 3.9 Ethylenedioxyphenyl) -5- Hz), 7.69 (s, 1H), 7.40 (s, 519 fluoro-N2- [3- (oxazole-2H), 7.31 (d, 1H, J = 2.4 Hz), il) -5-trifluoromethylphenyl] -7.19 (dd, 1H, J = 2.7 and 9.0 2,4-pMpdindianamine Hz), 6.72 (d, 1H, J = 8.4 Hz), 4.17 (s) , 4H); LCMS: purity: 92% 1 H NMR (DMSO-d 6): d 9.73 (s, 1H), 9.31 (s, 1H), 8.57 (s, 1H), 8.24 (s, 1H), N4- (3, 4- Dimethoxyphenyl) - 8.20 (bs, lH), 8.14 (d, 1H, J = 5-fluoro-N2- [3- (oxazole-4.2 Hz), 7.68 (s, 1H), 7.40 (s, 520 2-il) -5- + 1H), 7.33 (bdd, 1H, J = 9.0 trifluoromethylphenyl] -2.4-Hz), 7.23 (bs, 1H), 6.82 (d, pyrimidimethamine 1H, J = 7.5 Hz), 3.71 (s, 3H), 3.68 (s, 3H); LCMS: purity: 97 1 H NMR (DMSO-d 6): d 10.54 (s, 1 H), 9.70 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo- 9.42 (s, 1 H), 8.54 ( s, 1H), 4H-benz [1,4] oxazin-6- 8.27 (s, 1H), 8.21 (s, 1H), il) -5-fluoro-N2- [3- 8.16 (d, lH, J = 2.7 Hz), 7.67 521 (oxazol-2-yl) -5- (s, 1H), 7.40 (d, 1H), 7.33 trifluoromethylphenyl] -2,4- (bdd, 1H, J = 8.4 Hz), 7.17 pyrirmdmdiamine (d, 1H, J = 2.4 Hz), 6.81 (d, 1H, J = 8.4 Hz), 1.39 (s, 6H); LCMS: 1 H NMR (DMSO-d 6): d 9.55 (s, 1 H), 9.36 (s, 1 H), 9.30 (s, 1 H), 8.13 (m, 2 H), 5-Fluoro-N 4 - (3- 7.88 ( bd, 1H, J = 7.8 Hz), hydroxyphenyl) -N2- [3- 7.38 (t, 1H, J = 7.8 Hz), 7.27 522 (1, 2,4-oxadiazole-3 + (m, 2H), 7.13 (t, 1H, J = 7.8 ü) phenyl] -2.4-Hz), 7.02 (s, 1H), 6.50 (bdd, pyrip dindiamine 1H, J = 5.7 Hz); LCMS: purity: 95%; MS (m / e): 364 (M +).

No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 2-Chloro-5- fluoro-N4- 8.11 (d, 1H, J = 5.4 Hz), 6.79 methyl-N4- (3,4,5- (s, 2H), 3.74 (s, 3H), 3.72 (s, 523 trimethoxyphenyl) -4 - 3H), 3.65 (s, 3H), 3.38 (s, pyrimidinamine 3H); LCMS: purity: 94%, MS (m / e): 329 (MH +). 1 H NMR (DMSO-d 6): d 10.45 (s, 1 H), 9.59 (s, 1 H), 8.33 (s, 1 H), 8.21 (d, 1 H, J = 5-Fluoro-N 4 - (5- 2.7 Hz) , 8.18 (s, 1H), 7.83 methyl isoxazol-3-yl) -N2- (bd, 1H, J = 7.2 Hz), 7.55 524 + [3- (oxazol-2-yl) phenyl] - (bd, 1H, J = 8.1 Hz), 7.40 (t, 2,4-pyriridinediamine 1 H, J = 8.1 Hz), 7.35 (s, 1 H, J = 6.92 (s, 1 H), 2.29 9 s, 3 H); LCMS: purity: 100%, MS (m / e): 35 1 H NMR (DMSO-d 6): d 9.33 (s, 1H), 9.06 (s, 1H), 8.23 (s, 1H), 8.14 (bs, 1H ), 5-Fluoro-N4- (5-methyl-3- 8.09 (d, 1H, J = 3.6 Hz), 7.66 phenylisoxazol-4-yl) -N2- 525 (m, 3H), 7.43 (m, 4H) 7.32 [3- (oxazol-2-yl) phenyl] - (s, 1H), 7.24 (t, 1H, J = 7.2, 2,4-pyrimidinediamine, Hz), 2.36 (s, 3H); LCMS: purity: 85%, MS (m / e): 429 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 - (1-methyl-3-9.48 (m, 2H), 8.19 (m, 2H), phenylpyrazol-5-yl) -N 2 - [3- 8.11 ( , 2H), 7.77 (m, 2H), 526 + (oxazole-2-ü) phenyl] -2.4-7.35 (m, 6H), 6.73 (s, 1H), pyramidmidiamine 3.32 (s, 3H); LCMS: purity: 83%, MS (m / e): 428 (MH +). 1 H NMR (DMSO-d 6): d 9.89 (s, 1 H), 9.83 (s, 1 H), N 2, N 4 -Bis [3- 8.58 (s, 1 H), 8.49 (s, 1 H), methoxycarbonyl-5- 8.46 (s, 1H), 8.35 (s, 1H), 527 (oxazol-2-yl) phenyl] -5- 8.27 (d, 1H, J = 3.6 Hz), 8.08 + fluoro-2,4- (m, 3H ), 7.30 (s, 1H), 7.27 pyrimidine diamine (s, 3H), 3.71 (s, 3H), 3.68 (s, 3H); LCMS: purity: 86%, MS (M / e): 531 (MH +). 1 H NMR (DMSO-d 6): d 8.76 (s, 1 H), 8.13 (s, 1 H), N 2, N 4 -Bis (3.5-7.83 (d, 1 H, J = 3.9 Hz), 2.19 dimethylisoxazole-4- il) -5- 528 (s, 3H), 2.10 (s, 3H), 2.03 (s, fluoro-2,4- 3H), 1.85 (s, 3H); LCMS: pminidindiamine purity: 91%, MS (m / e): 319 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.99 (s, 1H) , 9.19 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H), N2, N4-Bis [3- (oxazol-2- 8.31 (d, 1H, J = 2.7 Hz), 8.11 ü) -5-trifluoromethylphenyl] -529 (d, 1H, J = 5.1 Hz), 8.05 (s, 5-fluoro-2,4- + 1H), 7.79 (s, 1H), 7.61 (s, pyrimidinediamine 1H), 7.31 (s, 1H), 7.27 (s, 1H); LCMS: purity: 92%, MS (m / e): 551 (MH +). 1 H NMR (DMSO-d 6): d 9.43 (s, 1 H), 9.23 (s, 1 H), N 2 - [(2-tert-Butyl-1, 3.4-8.25 (s, 1H), 8.08 (d, 1H, J = oxadiazole-5-ü) phenyl] -N4- 3.6 Hz), 7.93 (bd, 1H, J = 8.7 530 (3, 4-dimethoxyphenyl) -5-Hz), 7.49 9bd, 1H, J = 7.5 + + fluoro-2,4-Hz), 7.35 (m, 2H), 7.25 (d, pyrimidindiamine 1H, J = 2.4 Hz), 6.75 (d, 1H, J = 8.7 Hz), 3.70 (s, 3H), 3.66 (s, 3H), 1.37 (s, 9H). 1 H NMR (DMSO-d 6): d 9.45 (s, 1H), 9.19 (s, 1H), 8.25 (t, 1H, J = 1.8 Hz), 8.07 N2 - [(2-tert-Butyl-1, 3, 4- (d, 1H, J = 3.3 Hz), 7.87 (bd, oxadiazol-5-yl) phenyl] -N4- 1H, J = 2.4 Hz), 7.51 (bd, 1H, 531 (3,4-ethylenedioxyphenyl) -5- J = 7.8 Hz), 7.40 (m, 2H), fluoro-2,4- 7.16 (dd, 1H, J = 2.4 and 8.7 pyrimidinediamine Hz), 6.70 (d, 1H, J = 9 Hz), 4.15 (, 4H), 1.37 (s, 9H); LCMS: 1 H NMR (DMSO-d 6): d 9.45 (s, 1 H), 9.28 (s, 1 H), 9.23 (s, 1 H), 8.24 (s, 1 H), N 2 - [(2-tert-Butyl-1) , 3.4-8.11 (d, 1H, J = 3.9 Hz), 8.00 oxadiazol-5-yl) phenyl] -5- (bd, 1H, J = 8.1 Hz), 7.50 (d, 532 fluoro-N4- ( 3-1H, J = 7.8 Hz), 7.39 (t, 1H, hydroxyphenyl) -2.4- J = 8.4 Hz), 7.30 (bd, 1H, J = pijrimidindiamine 8.4 Hz), 7.12 (t, 1H, J = 2.1 Hz), 6.99 (t, 1H, J = 8.4 Hz), 6. 1 H NMR (DMSO-d6): d N4- (3.4- 7.61 (d, 1H, J = 5.4 Hz), 6.86 Ethylenedioxyphenyl) - 5- (m, 1H), 6.69 (, 2H), 4.29 533 fluoro-N4-methyl-2- (s, 4H), 3.51 (s, 3H); LCMS: hydrazine-4- purity: 90%, MS (m / e): 292 pyrimidine (MH +).

No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, LD, LD, llpt CELMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.35 (s, 1H) , 8.88 (s, 1H), 8.31 (s, 1H), 8.14 (s, 1H), N4- (3.5- 8.10 (d, 1H, J = 3.6 Hz), 7.71 Dimethylisoxazole-4-yl) -5 - (bd, 1H, J = 7.8 Hz), 7.45 (d, 534 fluoro-N2- [3- (oxazole-2H, J = 6.6 Hz), 7.32 (d, 1H, il) phenyl] -2, 4- J = 0.9 Hz), 7.29 (t, 1H, J = pyrimidinediamine 8.1 Hz), 2.87 (s, 3H), 2.10 (s, 3H); LCMS: purity: 96%, MS (m / N4- (3,5-Dimethylisoxazol-4-yl) -5-fluoro-N2- [5- LCMS: purity: 85%, EM 535 methoxycarbonyl-3- (m / e): 425 (MH +). + (oxazol-2-yl) phenyl] -2,4-pyrimid diamine 1 H NMR (DMSO-d 6): d 11.16 (s, 1H), 10.00 (s, 1H), salt of the p-toluene acid 9.52 (s, 1H), 8.16 (d, 1H, J = sulphonic of N2- (3.5-4.2 Hz), 7.46 (m, 2H), 7.35 Dimethyl-4-methoxyphenyl) - (d, 1H, J = 8.1 Hz), 7.13 (s, 536 N4- (2,2-dimethyl-3-oxo-2H), 7.08 (d, 1H, J = 2.4 Hz), 4H-5-pyrid [1.4] ] oxazin- 3.60 (s, 3H), 2.28 (s, 3H), 6-yl) -5-fluoro-2,4- 2.14 (s, 6H), 1.43 (s, 6H); pyrir dmdiamine CLEM: purity: 99%, MS (m / e): 439 1 H NMR (DMSO-d 6): d Salt of acid 11.19 (s, 1H), 10.52 (s, 1H), benzenesulfonic acid of N2- 9.65 (s, 1H), 8.19 ( d, 1 H, J = (3,5-Dimethyl-4- 4.5 Hz), 7.56 (m, 2 H), 7.44 methoxyphenyl) -N 4 - (2,2- (d, 1 H, J = 8.4 Hz), 7.35 ( d, 537 dimethyl-3-oxo-4H-5-1H, J = 8.4 Hz), 7.30 (m, pyrid [1,4] oxazin-6-yl) -5- 3H), 7.10 (s, 2H), 3.60 (s, fluoro-2,4-3H), 2.14 (s, 6H), 1.43 (s, pyrimidinediamine 6H); LCMS: purity: 93%, MS (m / e): 439 1 H NMR (DMSO-d 6): d Acid salt 11.80 (s, 1H), 10.16 (s, 1H), methanesulfonic acid of N2- 9.73 (s, 1H ), 8.21 (d, 1H, J = (3,5-Dimethyl-4- 4.2 Hz), 7.44 (d, 1H, J = 8.4 methoxyphenyl) -N4- (2.2-Hz), 7.36 (d, 1H , J = 8.4 Hz), 538 dimethyl-3-oxo-4H-5-7.12 (s, 2H), 3.60 (s, 3H),? Irid [1,4] oxazin-6-yl) -5-2.32 ( s, 3H), 2.13 (s, 6H), fluoro-2,4- 1.43 (s, 6H); LCMS: purity: pyridmidinediamine 97%, MS (m / e): 439 (MH +, per pair No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d P-10.67 (s, 1H), 10.60 (s, 1H), toluenesulfonic acid salt of N4- 10.05 (s, 1H), 8.20 (d, 1H) , J = (2,2-Dimethyl-3-oxo-4H- 4.8 Hz), 7.84 (s, 1H), 7.62 benz [1,4] oxazin-6-yl) -5- 539 (d, 1H, J = 9 Hz), 7.45 (bd, fluoro-N2- (2- 2H, J = 7.8 Hz), 7.23 (d, 1H, trifluoromethyl-3H- J = 8.7 Hz), 7.15 (s, 1H), 7.09 benzimidazole- 5-yl) -2.4- (d, 1H, J = 7.8 Hz), 6.85 (d, pyrimidiamine 1H, J = 8.7 Hz), 2.28 (s, 3H), 1 H NMR (DMSO-d6): d Salt of acid 10.66 (s, 1H), 10.20 (s, 1H), benzenesulfonic of N4- 9.90 (s, 1H), 8.17 (d, 1H, J = (2,2-Dimethyl-3-oxo-4H- 4.5 Hz ), 7.88 (s, 1H), 7.57 benz [1,4] oxazin-6-yl) -5- (m, 3H), 7.48 (d, 1H, J = 8.4 540 fluoro-N2- (2 Hz) , 7.29 (m, 4H), 7.15 (s, trifluoromethyl-3H-1H), 6.85 (d, 1H), J = 8.4 benzimidazol-5-yl) -2.4-Hz); LCMS: purity: 95%, pyrimidindiaraine MS (m / e): MH +, for original ion). 1 H NMR (DMSO-d 6): d Salt of acid 10.67 (s, 1H), 10.45 (s, 1H), methanesulfonic acid of N4- 10.19 (s, 1H), 8.23 (d, 1H, J = (2,2- Dimethyl-3-oxo-4H- 5.1 Hz), 7.80 (s, 1H), 7.62 benz [1, 4] oxazin-6-yl) -5- (d, 1H, J = 8.7 Hz), 7.45 (d, 541 fluoro-N2- (2-1H, J = 8.4 Hz), 7.11 9s, 1H), + trifluoromethyl-3H-6.85 (d, 1H, J = 8.4 Hz), 2.38 benzimidazol-5-yl) -2.4 - (s, 3H), 1.37 (s, 6H); LCMS: pyrirm-mydiamine purity: 99%, MS (m / e): 488 (M 1 H NMR (DMSO-d 6): d Hydrogen chloride salt 10.64 (s, 1H), 9.90 (s, 1H), of N4- (2,2-Dimetü-3- 9.80 (s, 1H), 8.15 (d, 1H, J = oxo-4H- 4.8 Hz), 7.96 (s, 1H), 7.59 benz [l, 4] oxazin-6- il) -5- (d, 1H, J = 8.7 Hz), 7.50 (dd, 542 fluoro-N2- (2-1H, J = 1.5 and 9.3 Hz), 7.25 trifluoromethyl-3H- (m, 2H), 6.87 (d, 1H, J = 8.4 benzimidazol-5-yl) -2.4-Hz); LCMS: purity: 99%, pyririne, indiamine MS (m / e): 488 (MH +, for original ion). (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-LCMS: purity: 98%; MS 43 il) -5-fluoro-N 2 - (3,4,5- (m / e): 470 (MH +); + trimethoxyphenyl) -2,4-pyrirm ^ indiamine N4- (2-Amino-3-methoxy-d-6-yl) -N2- (3,5-CLEM: purity: 92 %; MS 44 pyrim + dimethoxyphenyl) -5-fluoro- (m / e): 387 (MH +) 2,4-? Irimidindiamine No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (2-Amino-3-methoxypyrid-6-yl) -5- CLEM: purity: 94%; EM 545 fluoro-N2- (3,4,5 - + (m / e): 417 (MH +) trimethoxyphenyl) -2,4-pyrimidinediamine N 4 - (2-Amino-3-methoxy? irid-6-yl) -5-fluoro-N 2 - (2-CLEM: purity: 82 %; MS 546 methoxycarbonylbenzo- (m / e): 425 (MH +) furan-5-yl) -2,4-pyrimidinediamine N 4 - (2-Amino-3-methoxypyrid-6-yl) -5-fluoro-N 2 [3- (N-CLEM: purity: 89%; EM 547 + methylaminocarbonyl- (m / e): 414 (MH +) methyleneoxy) phenyl] -2,4-pyrimidiammine N 2 - (3,5-Dichloro-4-Mdroxyphenyl) -N 4 - (3,5-CLEM: purity: 92%; EM 548 dichloro-4-methoxyphenyl) - (m / e): 465 (MH +) 5-fluoro-2,4-pyrimidmdiamine N 4 - (4-Acetyl-2,2-dimethyl-3-oxo- pyrid [1,4] oxazin-6-yl) -5- LCMS: purity: 97%; EM 549 fluoro-N2- (3,4,5- (m / e): 513 (M +) trimethoxyphenyl) -2,4-pyrinidinediamine N 4-Acetyl-N 4 - (2,2-dimethyl-3-oxo-4H- ? irid [1,4] oxazin-6-yl) -5- LCMS: purity: 96%; EM 550 fluoro-N2- (3,4,5- (m / e): 513 (M +) trimethoxyphenyl) -2,4-pyrimidinediamine N 2-Acetyl-N 4 - (2,2-dimethyl-3-oxo-4H- pyrid [1,4] oxazin-6-yl) -5-LCMS: purity: 95%; 514 551 fluoro-N2- (3,4,5- (MH +) trimethoxyphenyl) -2,4-pyrimidindiaemia 2, N4-Bis [3-methyl-4- (4-methylpiperaziml) phenyl) -5- CLEM: purity: 99%; EM 552 fluoro-2,4- (m / e): 506 (MH +) pyrimidinediamine No. Compound Name Physical Data Triptase Triplase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt JH NMR (DMSO-d6): d 9.14 (bs, 1H), 9.04 (s, 1H), 8.06 N4- (3,5-Dimethylphenyl) -5- (d, J = 3.9 Hz, 1H) , 7.40-7.36 fluoro-N2- (3,4,5-553 (m, 2H), 6.95 (s, 2H), 6.67 trimethoxyphenyl) -2,4- (s, 1H), 3.58-3.56 (m, 9H ), pyrimidinediamine 2.19 (s, 6H); LCMS: purity: 96%; MS (m / e): 399 (MH +). * H NMR (DMSO-d6): d 9.21 (bs, 1H), 9.04 (bs, 1H), 8.63 (bs, 1H), 8.05 (d, J = 3.6 Hz, N2- (3-Chloro-4-hydroxy - 1H), 7.53-7.49 (m, 1H), 5-methylphenyl) -5-fluoro-554 7.34-7.30 (m, 2H), 7.24-7.20 N4- (3,5-dimethylphenyl) - (m, 1H) , 6.69 (bs, 1H), 2.22 2,4-pyriridinediamine (s, 6H), 2.09 (s, 3H); LCMS: purity: 93%; MS (m / e): 373 (MH +). * H NMR (DMSO-d6): d 9.11 (s, 2H), 8.06 (d, J = 3.9 Hz, N2- [3,5-Bis (hydroxy-1H), 7.45 (s, 2H), 7.38 (s) , methylene) phenyl] -N4- (3.5-555 2H), 6.85 (s, 1H), 6.68 (s, + dimethylphenyl) -5-fluoro- 1H), 4.38-4.34 (m, 4H), 2.22 2 , 4-pyrimidindiamine (s, 6H); LCMS: purity: 99%; MS (m / e): 369 (MH +). JH NMR (DMSO-d6): d 9.76 (bs, 1H), 9.51 (bs, 1H), 8.18 N2- (3,5-Dichlorophenyl) - (d, J = 3.9 Hz, 1H), 7.73-7.69 N4- (3,5-dimethylphenyl) -5- (m, 2H), 7.29-7.25 (m, 2H), 556 fluoro-2,4-7.04 (t, J = 1.8 Hz, 1H), 6.75 + + pyrimidinediamine (s) , 1H), 2.25 (s, 6H); LCMS: purity: 92%; MS (m / e): 378 (MH +). ? NMR (DMSO-d6): d 11.66 (s, 1H), 9.37 (s, 1H), N4- (3,5-Dimethylphenyl) -5- 9.28 (s, 1H), 8.48-8.40 (m, fluoro-N2) - [2- (N-1H), 8.13 (d, J = 3.6 Hz, 1H), 557 methylamin) carbonyl- 7.98-7.88 (m, 1H), 7.33 (s, 2H), indole-7-yl] - 2.4- 7.22 (d, J = 7.8 Hz, 1H), 7.04 (d, p? ± nidindiamine J = 1.8 Hz, 1H), 6.90 (t, J = 8.1 Hz. 1H), 6.71 (s, 1H) , 2.80 (d, J = 3.0Hz, 3H), 2 JH NMR (DMSO-d6): d 11.57 (s, 1H), 9.65 (s, 1H), 9.40 (s, 5-Fluoro-N4- (3- methoxy-1H), 8.39-8.35 (m, 1H), 8.15 (d, 5-trifluoromethylphenyl) - J = 3.9 Hz, 1H), 7.78 (d, J = 7.5 N2- [2- (N- 558 Hz, 1H ), 7.73-7.69 (m, 1H), methyamin) carbonyl- + 7.57-7.52 (, 1H), 7.18 (d, J = indol-7-yl] -2.4- 7.8 Hz, 1H), 9.98 (d) , J = 1.8 Hz, piri idindiamine 1H), 6.87-6.80 (m, 2H), 3.70 (s, 3H), 2.

No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt: H NMR (DMSO-d6): d 9.49 (s, 1H ), 9.21 (s, 1H), 9.19 (s, N2- (3,5-Dichloro-4-1H), 8.08 (d, J = 3.3 Hz, 1H), hydroxyphenyl) -N4- (3.5-559) 7.66 (d, J = 1.5 Hz, 2H), 7.29 dimethylphenyl) -5-fluoro- + (s, 2H), 6.70 (s, 1H), 2.24 (s, 2,4-pyrimidinediamine 6H); LCMS: purity: 95%; MS (m / e): 394 (MH +). ? NMR (DMSO-d6): d 9.17 (s, 1H), 9.13 (s, 1H), 8.07 (d, N2- (4-Chloro-3,5-J = 3.9 Hz, 1H), 7.45 (s, 2H ), dimethylphenyl) -N 4 - (3.5-560 7.30 (s, 2H), 6.72 (s, 1H), dimethylphenyl) -5-fluoro- 2.22 (s, 6H), 2.18 (s, 6H); 2,4-? Irimidindiamine CLEM: purity: 93%; MS (m / e): 372 (MH +). * H NMR (DMSO-d6): d 9.53 (s, 1H), 9.13 (s, 1H), 8.17- 8.12 (m, 1H), 8.11 (d, J = 3.9 N4- [3,4- (Difluoromethyl- Hz, 1H), 7.42 (dd, J = 2.4 and endioxy) phenyl] -5-fluoro- 9.0 Hz, 1H), 7.32 (d, J = 8.4 561 N2- (3,4,5-Hz, 1H), 7.00 (s, 2H), 3.64 + trimethoxyphenyl) -2,4- (s, 6H); 19 F NMR (282 pyridminediamine, DMSO-d 6): -49.77, -164.19; LCMS: purity: 93%; MS (m / e): 4 * H NMR (DMSO-d6): d 9.54 (s, 1H), 9.22 (s, 1H), 8.12 (d, J = 3.6 Hz, 1H), 8.11-8.08 N4- [ 3, 4- (Difluoromethyl- (, 1H), 7.42 (dd, J = 2.1 and endioxy) phenyl] -N2- (3.5-9.0 Hz, 1H), 7.32 (d, J = 8.7 562 + dimethoxifem) - 5-fluoro-Hz, 1H), 6.90 (d, J = 2.1 Hz, 2,4-pyrir-mydiamine 2H), 6.07 (t, J = 2.4 Hz, 1H), 3.65 (s, 6H); 19F NMR (282 MHz, DMSO-d6): -49.69, -16 * H NMR (DMSO-d6): d 9.51 (s, 1H), 9.13 (s, lH), 8.11 (d, J = 3.6 Hz, 1H ), 8.09-8.06 N4- [3, 4- (Difluoromethyl- (m, 1H), 7.39 (dd, J = 2.1 and endioxy) fenu] -N2- (3.5- 8.7 Hz, 1H), 7.34 (d , J = 9.0 563 dimethylphenyl) -5-fluoro-Hz, 1H), 7.22 (s, 2H), 6.53, 2,4-pyrimidinediamine (s, 1H), 2.16 (s, 6H); 19 F NMR (282 MHz, DMSO-d6): -49.67, -164.51; LCMS: purity: 98 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt lH NMR (DMSO-d6): d 9.59 (s, 1H), 9.45 (bs, 1H), 9.31 N2- (3,5-Dichloro-4- (s, 1H), 8.08 (d, J = 3.6 Hz, hydroxyphenyl) -N4- [3,4- 1H), 7.85-7.79 (m, 1H), 7.55 564 (difluoromethyl- (s, 1H), 7.29 (s, 1H); 19F, endioxy) phenyl] -5-fluoro-NMR (282 MHz, DMSO- 2.4 -pyrimidinediamine d6): -49.50, -163.68; LCMS: purity: 96%; MS (m / e): 446 (MH +). L NMR (DMSO-d6): d 9.62-9.68 (, 2H), 8.19 (d, J = 3.6 Hz, 1H), 7.92-7.88 N2- (3,5-Dichlorophenyl) - (, 1H), 7.71 (s) , 1H), 7.70 N4- [3, 4- (difluoromethyl- (s, 1H), 7.38-7.33 (m, 2H), 565 + endioxy) phenyl] -5-fluoro-7.00 (t, J = 1.8 Hz, 1 HOUR); 19F 2,4-pyrimidiamine NMR (282 MHz, DMSO-d6): -49.51, -162.64; LCMS: purity: 99%; MS (m / e): 430 (MH +). 'H NMR (DMSO-d6): d 9.84 N2- (4-Chloro-3,5- (s, 1H), 9.51 (s, 1H), 8.18 (s, dimethylphenyl) -N4- [3,4- J = 2.7 Hz, 1H), 7.99 (bs, 566 (difluoromethyl-1H), 7.41-7.35 (m, 4H), 2.22 endioxy) phenyl] -5-fluoro- (s, 6H); LCMS: purity: 2,4-pyriridinediamine 94%; MS (m / e): 424 (MH +). X H NMR (DMSO-d 6): d 9.57 (s, 1 H), 9.14 (s, 1 H), 8.58 N 2 - (3-Chloro-4-hydroxy- (bs, 1 H), 8.05 (d, J = 3.9 Hz, 5-methylphenyl) -N4- [3,4- 1H), 7.90 (s, 1H), 7.44 (d, J = 567 (drfluoromethyl- 1.8 Hz, 1H), 7.31 (dd, J = 1.8 + endioxy) fe l ] -5-fluoro- and 8.7 Hz, 1H), 7.26 (d, J = 8.4 2,4-pyrimidinediamine Hz, 1H), 7.14-7.09 (m, 1H), 2.06 (s, 3H); 19F NMR (282 MHz, DMSO-d6): -49.60, * H NMR (DMSO-d6): d 9.60 (s, 1H), 9.56 (s, 1H), 8.17 (d, J = 3.3 Hz, 1H), 8.00 (s, 1H), N4- [3,4- (Difluoromethyl- 7.66 (s, 1H), 7.52 (s, 1H), endioxy) phenyl] -5-fluoro-7.41-7.31 (m, 2H), 6.72. (s, 568 N2- (3-methoxy-5-1H), 3.74 (s, 3H); 19F NMR trifluoromethylphenyl) -2.4- (282 MHz, DMSO-d6): - pyrimidinediamine 49.75, -61.96, -162.93; LCMS: purity: 93%; MS (m / e): 459 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, ID, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Tone, 3pt! H NMR (DMSO-d6): d 9.66 (s, 1H ), 9.59 (s, 1H), 8.19 (d, J = 3.6 Hz, 1H), 8.04-7.97 N4- [3,4- (Difluoromethyl- (m, 1H), 7.84 (bs, 1H), 7.68 endioxy) phenyl] -5-fluoro- (bs, 1H), 7.36 (bs, 2H), 7.03 569 N2- (3-methyl-5- (s, 1H), 2.29 (s, 3H); 19F + trifluoromethylfenu) -2,4- NMR (282 MHz, DMSO- pyrimidinediamine d6): -49.63, -61.86, -163.10; LCMS: purity: 98%; MS (m / e): 443 (MH 1 H NMR (DMSO-d 6): d 11.56 (s, 1H), 9.63 (s, 1H), N 4 - [3,4- (Difluoromethyl- 9.34 (s, 1H), 8.44-8.38 (m, endioxy) phenyl] -5-fluoro-1H), 8.12 (d, J = 3.6 Hz, 1H), N2- [2- (N- 7.97 (bs, 1H), 7.84-7.78 (, 570 methylamin) carbonyl- 1H), 7.38-7.32 (m, 1H), 7.26 indole-7-yl] -2,4- (d, J = 9.0 Hz, 1H), 7.20 (d, pyramide indiamine J = 8.1 Hz, 1H), 7.00 (s, 1H), 6.87 (t, J = 7.8 Hz, 1H), 2.74 (! H RNM (DMSO-d6): d 9.28 (s, 1H), 9.03 (s, 1H), 8.15- N4- (3-Chloro-4- 8.07 (m, 1H), 8.05 (d, J = 3.3 methoxyphenyl) -N2- [3.5-Hz, 1H), 7.76-7.72 (m, 2H), dimethyl -4- (N- 7.68-7.60 (m, 1H), 7.23 (s, 571 methylamin) carbonyl- + 2H), 7.09 (d, J = 9.0 Hz, 1H), methylenexypheniTJ-5- 4.10 (s, 2H) 3.83 (s, 3H), fluoro-2,4- 2.69 (d, J = 4.2 Hz, 3H), 2.11 pyrirmdmdiamine (s, 6H), CLEM: purity: 99%,: H RNM (DMSO-d6): d 9.08 (s, 1H), 8.95 (s, 1H), 8.14- N2- [3,5-dimetü-4- (N- 8.06 (m, 1H), 8.00 (d, J = 3.6 methylamin) carbonyl- Hz , 1H), 7.23-7.25 (m, 3H), methylenexyphenyl] -N4- 7.20-7.14 (m, 1H), 6.78 (d, 572 + + (3,4-ethylenedioxyphenyl) -5- J = 8.7 Hz, 1H), 4.21 (s, 4H), fluoro-2,4- 4.11 (s, 2H), 2.69 (d, J = 4.5 pyriridinediamine Hz , 3H), 2.13 (s, 6H); LCMS: purity: 99%; MS (m / e): 454 'H NMR (DMSO-d6): d 9.20 (s, 1H), 9.01 (s, 1H), 8.14- N4- (3, 5-dimethoxyphenyl) -8.05 (m, 2H) , 7.29 (s, 2H), N2- [3,5-dimethyl-4- (N- 7.00-6.96 (m, 2H), 6.24-6.19 methanamine) carbonyl- 573 (m, 1H), 4.11 (s, 2H) ), 3.67 methyleneoxyphenyl] -5- + (s, 6H), 2.70 (d, J = 4.8 Hz, fluoro-2,4- 3H), 2.12 (s, 6H); LCMS: pyrylimidiamine purity: 99%; MS (m / e): 456 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt! H NMR (DMSO-d6): d 10.59 (s, 1H ), 9.32 (s, 1H), N2- [3,5-dimethyl-4- (N- 8.95 (s, 1H), 8.11-8.06 (, methylamino) carbonyl- 1H), 8.04 (d, J = 3.9 Hz , 1H), methylenexyphenyl] -N4- 7.34-7.23 (, 3H), 7.21-7.18 574 (2,2-dimethyl-3-oxo-4H- + (m, 1H), 6.87 (d, J = 9.0 Hz, benz [1,4] oxazin-6-yl) -5- 1 H), 4.10 (s, 2H), 2.69 (d, J = fluoro-2,4- 4.8 Hz, 3H), 2.11 (s, 6H), pyrimidinediamine 1.40 (s, 6H); LCMS: purity: 95%; H NMR (DMSO-d6): d 9.15 (s, 1H), 8.96 (s, 1H), 8.12- N2- [3,5-dimethyl-4- (N-8.05 (m, 1H), 8.01 (d , J = 3.9 methyamin) carbonyl-Hz, 1H), 7.44-7.40 (m, 1H), methylenexyphenyl] -5- 7.25 (s, 2H), 7.15-7.07 (m, 575 + fluoro-N4- (3.4 - 1H), 6.84 (d, J = 8.1 Hz, 1H), methylenedioxyphenyl) -2.4- 5.98 (s, 2H), 4.11 (s, 2H), pyrimidinediamine 2.69 (d, J = 4.8 Hz, 3H), 2.13 (s, 6H); LCMS: purity: 99%; 1 H NMR (DMSO-d 6): d 8.17 (d, J = 2.7 Hz, 1H), 8.14 (d, J = 5.4 Hz, 1H), 7.74 (dd, 2-Chloro-5-fluoro-N4- (2- J = 2.7 and 8.7 Hz, 1H), 6.77 isopro? Oxy? Irid-5-yl) - 576 (dd, J = 0.6 and 8.7 Hz, 1H), N4-methyl-4- 5.21 (quintet, J = 6.3 Hz , 1H), pyrirnidinamine 3.38 (s, 3H), 1.29 (d, J = 6.3 Hz, 6H); LCMS: purity: 95%; MS (m / e): 298 (MH +). 1 H NMR (DMSO-d 6): d 7.95 (d, J = 5.7 Hz, 1H), 7.46 (d, J = 2.7 Hz, 1H), 7.28 (dd, N4- (3-Chloro-4-J = 2.4 and 9.0 Hz, lH), 7.13 (d, methoxyphenyl) -N2- (3.5-J = 9.0 Hz, 1H), 6.98 (s, 1H), 577 dimethoxypheni) -5-fluoro-6.97 (s, 1H), 6.09-6.06 (m, N 4 -methyl-2,4- 1 H), 3.86 (s, 3 H), 3.69 (s, pyrimidineamine 6H), 3.44 (s, 3H); LCMS: purity: 96%; MS (m / e): 419 (MH + 1 H NMR (DMSO-d 6): d 9.41 (s, 1 H), 7.99 (d, J = 6.3 N 2 - (3-Chloro-4-methoxy-Hz, 1 H), 7.69 (d, J = 2.7 Hz, 5-methylphenyl) -N4- (3-1H), 7.47 (d, J = 2.4 Hz, 1H), 578 chloro-4-methoxyphenyl) -5- 7.36 (d, J = 1.8 Hz, 1H), 7.28 + fluoro-N4-methyl-2,4- (dd, J = 2.7 and 8.7 Hz, 1H), pyrimidindiamiaa 7.14 (d, J = 8.7 Hz, 1H), 3.87 (s, 3H), 3.68 (s, 3H), 3.42 (s, 3H), 2.19 (s, 3H), CLEM: No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-dd): d 9.24 (s, 1H), 8.16-8.04 (m, N4- (3-Chloro-4-methoxifem) -N2- [3.5-1H), 7.96 (d, J = 6.0 Hz, 1H), 7.47 (d, J = 2.4 Hz, 1H ), dimethyl-4- (N- 7.31-7.24 (m, 3H), 7.15 (d, 579 methylamin) carbonyl- J = 8.7 Hz, 1H), 4.12 (s, 2H), methylenexyphenyl] -5- 3.87 (s) , 3H), 3.42 (s, 3H), fluoro-N 4 -methyl-2,4- 2.69 (d, J = 4.8 Hz, 3H), 2.15 pyrjimidinediamine (s, 6H); LCMS: purity: 92%; MS (m / e 1 H NMR (DMSO-d 6): d 9.63 (bs, 1H), 8.02 (d, J = 6.3 N4- (3-Chloro-4-Hz, 1H), 8.00-7.97 (m, 1H) , methoxyphenyl) -N2- [3- (N- 7.50 (d, J = 2.7 Hz, 1H), methyamin) carbonyl- 7.36-7.34 (, 1H), 7.33-7.20 580 methylenexyphenyl] -5- (m, 3H) , 7.16 (d, J = 9.0 Hz, + fluoro-N4-methyl-2,4-2H), 6.57-6.52 (m, 1H), 4.41 pyrimidinediamine (s, 2H), 3.87 (s, 3H), 3.44 ( s, 3H), 2.64 (d, J = 4.8 Hz, 3H), L 1H NMR (DMSO-d6): d 9.47 (bs, 1H), 8.14 (d, J = 2.7 N2- (3,5-Dimethoxyfenu) - Hz, 1H), 7.99 (d, J = 6.0 Hz, 5-fluoro-N4- (2-1H), 7.71 (dd, J = 3.0 and 8.7 581 isopropoxypyrid-5-yl) - Hz, 1H), 6.96 -6.93 (m, 2H), + N4-methyl-2,4- 6.77 (dd, J = 0.6 and 8.7 Hz, pijrimidinadiamine 1H), 6.12 (t, J = 2.1 Hz, 1H), 5.21 (quintet, J = 6.3 Hz, 1H), 3.70 (s, 6H), 3.45 (s, 3H) 1H NMR (DMSO-d6): d 9.53 (s, 1H), 8.14 (d, J = 3.0 5-Fluoro-N4- (2 - Hz, 1H), 8.02-7.93 (m, 2H), isopropoxypyrid-5-yl) - 7.70 (dd, J = 2.7 and 8.7 Hz, N4-methyl-N2- [3- (N- 582 1H), 7.37 (t, J = 2.1 Hz, 1H), methylamino) carbonyl- 7.26-7.20 (m, 1H), 7 .13 (t, J = methylenexyphenyl) -2.4- 8.1 Hz, 1H), 6.78 (d, J = 8.7 pyrimidinediamine Hz, 1H), 6.56-6.50 (, 1H), 5.22 (quintet, J = 6.0 Hz, 1 H) 1 H NMR (DMSO-d 6): d 9.42 (s, 1 H), 8.14 (d, J = 2.7 N 2 - (3,5-Dimethylphenyl) -5 Hz, 1 H), 8.01 (d, J = 6.6 Hz , fluoro-N4- (2-1H), 3.45 (s, 3H), 2.19 (s, 583 isopro-oxypyrid-5-yl) - 6H), 1.29 (d, J = 6.3 Hz, 6H), N4-methyl -2.4- 7.70 (dd, J = 2.7 and 8.7 Hz, pyrin-Tidinadiamine 1H), 7.24 (s, 2H), 6.77 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 5.22 (quintet, J = 6.3 Hz, 1H); No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.09 (s, 1H) , 7.94 (d, J = 6.0 N4- (3-Chloro-4-Hz, 1H), 7.45 (d, J = 2.1 Hz, methoxyphenyl) -N2- (3, 5-1H), 7.31-7.23 (m, 3H), 7.13 584 dimethylphenyl) -5-fluoro- (d, J = 9.0 Hz, 1H), 6.51 (s, + N4-methyl-2,4- 1H), 3.86 (s, 3H), 3.42 (s, pyrimidimediamine 3H), 2.18 (s, 6H); LCMS: purity: 88%; MS (m / e): 387 (MH +). 1 H NMR (DMSO-d 6): d 9.45 (s, 1 H), 8.16 (d, J = 1.8 N 4 - (3-Chloro-4 Hz, 1 H), 8.05 (d, J = 6.0 Hz, methoxyphenyl) -5 -fluoro- 1H), 7.68 (dd, J = 2.1 and 9.0 N2- (2-585 Hz, 1H), 7.65 (d, J = 0.9 Hz, methoxycarbonylbenzo-1H), 7.63-7.57 (m, 1H), 7.54 furan-5-yl) -N4-methyl- (d, J = 2.7 Hz, 1H), 7.35 (dd, 2,4-puimidindiamine J = 2.7 and 8.7 Hz, 1H), 7.23 (d, J = 8.7 Hz, lH), 3.95 (s, 1 H NMR (DMSO-d 6): d; 9.39 (s, 1 H), 8.13 (d, J = 2.4 5-Fluoro-N 4 - (2 Hz, 1 H), 8.09 (d, J = 1.8 Hz, isopropoxypyrid-5-yl) - 1H), 7.98 (d, J = 6.3 Hz, 1H), N2- (2-586 7.70 (dd, J = 3.0 and 8.7 Hz, + methoxycarbonylbenzo-1H), 7.64 -7.57 (m, 2H), 7.54 furan-5-yl) -N4-metii- (d, J = 8.7 Hz, 1H), 6.79 (d, 2,4-pyrimidinediamine J = 8.7 Hz, 1H), 5.22 ( quintet, J = 6.3 Hz, 1H), 3.87 (s, 1H NMR (DMSO-d6): d 9.44 (bs, 1H), 8.03 (d, J = 6.0 Hz, 1H), 7.40 (d, J = 8.1 Hz , N4- (4-Chloro-3-1H), 7.15 (d, J = 2.1 Hz, 1H), methoxyphenyl) -N2- (3.5-6.95 (d, J = 1.2 Hz, 2H), 6.90 587 dimethoxyphenyl ) -5-fluoro- (dd, J = 2.1 and 8.4 Hz, 1H), + N4-methyl -2.4- 6.12-6.08 (m, 1H), 3.82 (s, p? Imidindiamine 3H), 3.69 (s, 6H), 3.49 (s, 3H); LCMS: purity: 96%; MS (m 1 H NMR (DMSO-d 6): d 9.35 (bs, 1H), 8.03 (d, J = 6.0, 1H), 7.41 (d, J = 8.4, 1H), N4- (4-Chloro-3-) 7.26-7.23 (m, 2H), 7.16 (d, methoxyphenyl) -N2- (3, 5- J = 2.4 Hz, 1H), 6.90 (dd, J = 588 dimethylphenyl) -5-fluoro- + 2.1 and 8.7 Hz , 1H), 6.58-6.55 N4-methyl-2,4- (m, 1H), 3.82 (s, 3H), 3.49 pyrimidiamine (s, 3H), 2.19 (s, 6H), LCMS: purity: 91%; MS (m / e): 387 (MH + No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6 ): d 9.34 (s, 1H), 8.00 (d, J = 5.4, N4- (4-Chloro-3-1H), 7.93-8.00 (m, 1H), 7.44 methoxyphen) -5 ~ fluoro- (t, J = 1.8 Hz, 1H), 7.39 (d, N4-methyl-N2- [3- (N- 589 J = 8.4 Hz, 1H), 7.26 (dd, J = + methylamin) carbonyl- + 1.2 and 8.4 Hz, 1H), 7.15-7.12 methylenexyphenyl] -2,4- (m, 1H), 7.09 (d, J = 8.4 Hz, pyrimidinediamine 1H), 6.87 (dd, J = 2.1 and 9.0 Hz, 1H), 6.47 (dd, J = 2.7 1 H NMR (DMSO-d 6): d 10.84 (s, 1 H), 9,010 (s, 1 H), 7.96 (d, J = 5.4 Hz, 1 H), N 4 - (4-Chloro-3-7.87-7.84) (m, 1H), 7.39 (d, methoxyphenyl) -5-fluoro- J = 8.1 Hz, 1H), 7.27-7.19 590 N2- (indol-5-yl) -N4- + + (m, 3H), 7.12 (d, J = 2.1 Hz, methyl-2,4- 1H), 6.87 (dd, J = 2.4 and 8.7 pyriridinediamine Hz, 1H), 6.29-6.25 (m, 1H), 3.82 (s, 3H), 3.47 ( s, 3H); LCMS: puri 1H NMR (DMSO-d6): d 9.51 (bs, 1H), 8.03 (d, J = 6.0 N4- (4-Chloro-3,5-Hz, 1H), 7.19 (s, 2H), 6.93 dimethylphenyl) -N2- (3.5- (d, J = 1.8 Hz, 2H), 6.12 (t, 591 dimethoxyphenyl) -5-fluoro- + J = 2.4 Hz, 1H), 3.70 (s, 6H), N4 -methyl-2,4- 3.46 (s, 3H), 2.32 (s, 6H); pyrimimadiamine CLEM: purity: 98%; MS (m / e): 418 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (4-Chloro-3,5-9.49 (bs, 1H), 8.04 (d, J = 6.0 dimethylphenyl) -N 2 - (3,5-Hz, 1H), 7.24 (s, 2H), 7.20 592 dimethylphenyl) -5-fluoro- (s, 2H), 6.60 (s, 1H), 3.45 (s, N4-methyl-2,4- 3H), 2.32 (s, 6H), 2.19 (s, pmrm ^ diamine 6H); LCMS: purity: 98%; MS (m / e): 386 (MH +). 1 H NMR (DMSO-d 6): d 9.32 (s, 1 H), 7.98 (d, J = 5.7 N 4 - (4-Chloro-3,5-Hz, 1 H), 8.00-7.92 (m, 1 H), dimethylphenyl) -5-fluoro- 7.44 (t, J = 2.1 Hz, 1H), 7.29- N4-methyl-N2- [3- (N- 7.23 (, 1H), 7.16 (s, 2H), 593 methyl) carbonyl- 7.10 (t, J = 8.1 Hz, 1H), 6.47 + + methylenexyphenyl] -2,4- (dd, J = 2.4 and 7.8 Hz, 1H), pyrirmdmdiamine 4.39 (s, 2H), 3.44 (s, 3H), 2.64 (d, J = 4.5 Hz, 3H), 2.32 (No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.84 (s, 1H), 8.98 (s, 1H), N4- (4-Chloro-3,5-7.94 (d, J = 5.7 Hz, 1H), 7.84 dimethylphenyl) -5- fluoro- (s, 1H), 7.29-7.19 (m, 3H), 594 N2- (indol-5-yl) -N4- + 7.15 (s, 2H), 6.26 (t, J = 2.1 + methyl-2, 4- Hz, 1H), 3.42 (s, 3H), 2.32 pyrimidinediamine (s, 6H); LCMS: purity: 94%; MS (m / e): 397 (MH +). 1 H NMR (DMSO-d 6): d 9.43 (s, 1 H), 8.17 (d, J = 1.8 N 4 - (4-Chloro-3,5-Hz, 1 H), 8.01 (d, J = 5.4 Hz, dimethylphenyl) -5-fluoro- 1H), 7.68-7.61 (m, 2H), 7.55, _, N2- (2-methoxycarbonyl- (d, J = 9.3 Hz, 1H), 7.17 (s, benzofuran-5-yl) - N4-2H), 3.87 (s, 3H), 3.45 (s, methyl-2,4- 3H), 2.32 (s, 6H),; LCMS: pyr? M ^ indiamina purity: 97%; MS (m / e): 457 (MH +). 1 H NMR (DMSO-d 6): d 9.66 (s, 1 H), 8.11 (d, J = 0.90 N 4 - (4-Chloro-3,5-Hz, 1 H), 8.04 (d, J = 5.4 Hz, dimethylphenyl) -5-fluoro-1H), 7.81 (s, 4H), 7.28 (d, J = 596 N4-methyl-N2- [4- (oxazole-0.6 Hz, 1H), 7.18 (s, 2H), 2-ü phenyl] -2.4- 3.46 (s, 3H), 2.33 (s, 6H); pyrimidinediamine LCMS: purity: 89%; MS (m / e): 425 (MH +). 1 H NMR (DMSO-d 6): d 9.71 (s, 1 H), 8.40 (s, 1 H), N 4 - (4-Chloro-3,5- 8.24-8.18 (m, 1 H), 8.06 (d, dimethylphenyl) - 5-fluoro- J = 6.0 Hz, 1H), 7.59-7.53 597 N4-methyl-N2- [3- (oxazole- (, 2H), 7.34-7.29 (m, 2H), 5-yl) phenyl] -2 , 4- 7.20 (s, 2H), 3.49 (s, 3H), p? Ipüdmdiamiaa 2.32 (s, 6H); LCMS: purity: 96%; MS (m / e): 425 (MH +). 1 H NMR (DMSO-d 6): d 9.64 (s, 1 H), 8.35 (s, 1 H), 8.04 (d, J = N 4 - (4-Chloro-3,5-7.5 Hz, 1 H), 7.76 (d, J = 8.7 Hz, dimethylfer l) -5-fluoro-2H), 7.57 (d, J = 8.7 Hz, 2H), 598 N4-methyl-N2- [4- (oxazole-7.49 (s, 1H), 7.19 ( s, 2H), 3.46 5-ü) phenyl] -2.4- (s, 3H), 2.32 (s, 6H); LCMS: p-imidmdiamine purity: 96%; MS (m / e): 425 (MH +). lH NMR (DMSO-d6): d 11.00 (s, 1H), 9.58 (bs, 1H), 8.00 (d, N4- (4-Chloro-3.5-J = 6.0 Hz, 1H), 7.89 (s, 1H ), dimethylphenyl) -5-fluoro- 7.41 (d, J = 8.4 Hz, 1H), 7.24-99 N2- (indol-6-yl) -N4- 7.18 (m, 3H), 7.11 (dd, J = 1.8 and methyl-2,4- 8.4 Hz, lH), 6.35-6.31 (m, 1H), pyrimidinediamine 3.47 (s, 3H), 2.33 (s, 6H); LCMS: purity: 95%; MS (m e): 397 (MH +).

No. Name of Compound Physical Data Triptase Tftasa Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.94 (bs, 1H) , 9.65 (bs, 1H), N4- [3-Chloro-4- (N- 8.18 (d, J = 4.2 Hz, 1H), methylamino) carbonyl- 7.93-7.84 (m, 1H), 7.74 (d, methyleneoxyphenyl) ] -N2- J = 2.4 Hz, 1H), 7.66 (dd, J = 600 (3,5-dimetiphenyl) -5- 2.7 and 9.0 Hz, 1H), 7.12 (s, + fluoro-2,4- 2H) , 6.99 (d, J = 9.0 Hz, 1H), pijrirmdindiamine 6.64 (s, 1H), 4.55 (s, 2H), 2.66 (d, J = 4.8 Hz, 3H), 2.18 (s, 1H NMR (DMSO-d6 ): d 9.52 (bs, 1H), 9.30 (bs, 1H), N4- [3-Chloro-4- (N- 8.11 (d, J = 3.9 Hz, 1H), methylamino) carbonyl- 7.92-7.85 (m , 1H), 7.79 (d, methyleneoxyphenyl) -N2- J = 2.4 Hz, 1H), 7.74 (dd, J = 601 (3,5-dimethoxylfeml) -5- + 2.7 and 8.7 Hz, 1H), 6.96 (d , J = fluoro-2,4- 9,0 Hz, 1H), 6.85 (d, J = 1.8 pyrimidindiamine Hz, 2H), 6.10 (t, J = 2.4 Hz, 1H), 4.54 (s, 2H), 3.64 (s) , 6H) 1 H NMR (DMSO-d 6): d 9.45 (bs, 1H), 9.25 (bs, 1H), N 2 - (3-Chloro-4- 8.03 (d, J = 3.3 Hz, 1H), methoxy enyl) -N4- [3- 7.86-7.78 (m, 1H), 7.70 (d, chloro-4- (N- J = 2.4 Hz, 1H), 7.64 (d, J = 602 methyamin) carbonyl- 2.4 Hz, 1H), 7.58 (dd, J = 2.7 methyleneoxyphenyl) -5- and 9.3 Hz, 1H), 6.96 (d, J = 9.3 fluoro-2.4-Hz, 1H), 6.93 (d, J = 9.3 Hz, pirinn ^ mdiapiine 1H), 4.48 (s, 2H), 3.73 (s, 3H) 1H NMR (DMSO-d6): d 9.45 (bs, 1H), 9.2 = 8 (bs, N2- (4-Chloro-3,5 - 1H), 8.11 (d, J = 3.9 Hz, 1H), dimethylfeml) -N4- [3- 7.92-7.87 (m, 1H), 7.75 (d, chloro-4- (N- J = 2.4, 1H) , 7.68 (dd, J = 2.7 603 methyamin) carbonyl- and 9.3 Hz, 1H), 7.40 (s, 2H), methylenexyphenyl] -5-6.99 (d, J = 8.7 Hz, 1H), 4.54 fluoro-2.4 - (s, 2H), 2.67 (d, J = 4.2 Hz, pyrimidinediamine 3H), 2.22 (s, 6H),; LCMS: pur 1 H NMR (DMSO-d 6): d 9.42 (s, 1 H), 8.46-8.43 (m, N 4 - (4-Chloro-3,5- 1 H), 8.39-8.37 (m, 1 H), 8.00 dimethylphenyl ) -5-fluoro- (d, J = 5.4 Hz, 1H), 7.73 (d, 604 N4-methyl-N2- [4- (oxazole-J = 9.0 Hz, 2H), 7.62 (d, J = 4- il) phenyl] -2.4-9.0 Hz, 2H), 7.17 (s, 2H), pyrimidinediamine 3.45 (s, 3H), 2.32 (s, 6H); LCMS: purity: 96%; MS (m / e): 424 (MH +).

No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.80 (s, 1H) , 9.26 (s, 1H), 9.07 (s, 1H), 8.06 (s, J = 3.9 N4- [3-Chloro-4- (N-Hz, 1H), 7.93-7.75 (m, 4H), methylamin) carbonyl- 7.36 (d, J = 8.4 Hz, 1H), 605 methyleneoxyphenyl] -5 - 7.22-7.15 (m, 2H), 6.95 (d, fluoro-N2- (indol-6-yl) - J = 8.7 Hz, 1H), 6.33-6.27 2,4-pyrimidiamine (m, 1H), 4.54 (s, 2H), 2.67 (d, J = 4.2 Hz, 3H); LCMS: purity: 96%; M 1 H NMR (DMSO-d 6): d 9.44 (s, 1 H), 8.44 (d, J = 0.90 N 4 - (4-Chloro-3 Hz, 1 H), 8.38 (d, J = 0.90 Hz, methoxyphenyl) - 5-fluoro-1H), 8.02 (d, J = 5.7 Hz, 1H), 606 N4-methyl-N2- [4- (oxazole-7.73 (d, J = 8.7 Hz, 2H), 7.63 + + + 4- il) phenyl] -2,4- (d, J = 8.7 Hz, 2H), 7.41 (d, pü-imidmdiamine J = 8.4 Hz, 1H), 7.14 (d, J = 2.4 Hz, 1H), 6.92-6.86 (m, lH), 3.83 (s, 3H), 3.49 (s, 3 1H NMR (DMSO-d6): d 9.70 (bs, 2H), 8.23-8.18 (m, N4- (4-Chloro-3-1H ), 8.15 (d, J = 4.2 Hz, 1H), methoxifeml) -N2- [4- 7.71 (d, J = 2.7 Hz, 1H), 7.54 chloro-3- (N- 607 (dd, J = 2.7 y 9.0 Hz, 1H), methylamino) carbonyl- 7.45 (dd, J = 2.4 and 8.7 Hz, feml] -5-fluoro-2,4- 1H), 7.35 (d, J = 2.4 Hz, 1H), pyrMdindiamine 7.28 ( d, J = 8.7 Hz, 1H), 7.24 (d, J = 9.0 Hz, 1H), 3.73 (s 1H NMR (DMSO-d6): d 9.53 (bs, 1H), 9.49 (bs, 1H), N4- [3-Chloro-4- (N- 8.28-8.21 (m, 1H), 8.13 (d, methylamino) carbonyl- J = 3.9 Hz, 1H), 7.93-7.87 methylenexyphenyl] -N2- [4- (m, 1H ), 7.77-7.64 (m, 4H), 608 chloro-3- (N- 7.28 (d, J = 8.7 Hz, 1H), 6.98 methyamin) carbo nil- (d, J = 9.0 Hz, 1H), 4.59 (s, phenyl] -5-fluoro-2,4-2H), 2.70 (d, J = 4.8 Hz, 3H), pyrimidinediamine 2.67 (d, J = 4.5 Hz, 3H); LCMS: pu 1 H NMR (DMSO-d 6): d 9.84 (s, 1H), 9.59 (s, 1H), N 2 - [4-Chloro-3- (N- 8.35-8.27 (m, 2H), 8.23 (d , methylamino) carbonyl- J = 3.9 Hz, 1H), 8.06 (d, J = phenyl] -N4- (4-chloro-3-7.7 Hz, 1H), 7.75 (d, J = 2.4 609 trifluoromethylphenyl) -5- Hz, 1H), 7.67-7.60 (m, 2H), fluoro-2,4- 7.29 (d, J = 9.0 Hz, 1H), 2.71 pyrimidinediamine (d, J = 4.5 Hz, 3H); LCMS: purity: 92%; MS (m / e): 475 (MH +).

No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.55 (s, 1H) , 8.30-8.24 (m, N4- (4-Chloro-3,5-1H), 8.01 (d, J = 6.6 Hz, 1H), dimethylphenyl) -N2- [4- 7.86 (d, J = 2.7 Hz, 1H), 7.68 chloro-3- (N- (dd, J = 2.7 and 9.0 Hz, 1H), 610 methyamin) carbonyl- 7.27 (d, J = 8.7 Hz, 1H), 7.16 feml] -5-fluoro-N4 - (s, 2H), 3.42 (s, 3H), 2.72 (d, methyl-2,4- J = 4.5 Hz, 3H), 2.32 (s, 6H); pyrimid diamine CLEM: purity: 98%; MS (m 1 H NMR (DMSO-d 6): d 9.57 (s, 1 H), 9.54 (s, 1 H), N 4 - (4-Chloro-3- 8.19 (d, J = 3.6 Hz, 1 H), methoxyphenyl) - N2- [3- 8.15-8.08 (m, 1H), 7.93 (d, fil chloro-4- (N- J = 2.1 Hz, 1H), 7.51 (dd, J = methylamin) carbonyl- 2.4 and 8.7 Hz, 1H ), 7.47 (dd, + + phenyl] -5-fluoro-2,4- J = 2.45 and 8.7 Hz, 1H), 7.43 pyrimidinediamine (d, J = 2.1 Hz, 1H), 7.34 (d, J = 8.7 Hz , 1H), 7.27 (d, J = 8.4 Hz 1H NMR (DMSO-d6): d 9.83 (s, 1H), 9.65 (s, 1H), N2- [3-Chloro-4- (N- 8.33-8.26 (, 1H), 8.25 (d, methylamino) carbor? Il- J = 3.6 Hz, 1H), 8.16-8.11 phenyl] -N4- (4-chloro-3- (m, 1H), 8.06 (d, J = 2.7 Hz, 612 trifluoromethylphenyl) -5- 1H), 7.87 (d, J = 1.8 Hz, 1H), + fluoro-2,4- 7.66 (d, J = 8.7 Hz, 1H), 7.52 pyrimidinediamine (dd, J = 1.8 and 8.4 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 2.72 (d, 1H NMR (DMSO-d6): d 9.66 (s, 1H), 8.17-8.09 (, N4- (4- Chloro-3,5- 1H), 8.05 (d, J = 5.4 Hz, 1H), dimethylphenyl) -N2- [3- 7.94 (d, J = 2.1 Hz, 1H), 7.54 chloro-4-OSi- (dd , J = 2.1 and 8.4 Hz, 1H), 13 methylamin) carboml- 7.28 (d, J = 8.1 Hz, 1H ), 7.18 phenyl] -5-fluoro-N4- (s, 2H), 3.44 (s, 3H), 2.71 (d, methyl-2.4- J = 4.5 Hz, 3H), 2.32 (s, 6H); pyrimidinediamine LCMS: purity: 99%; MS (m / 1 H NMR (DMSO-d 6): d 10.28 (s, 1 H), 10.05 (s, 1 H), N 4 - [3-Chloro-4- 8.26 (d, J = 4.8 Hz, 1 H), 7.74 ( methoxycarbonyl) methyl- (d, J = 2.7 Hz, 1H), 7.57 (dd, 14 enoxyphenyl) -N2- (3.5- J = 2.7 and 8.7 Hz, 1H), 7.10- + + + dimethylphenyl) -5- fluoro- 7.01 (m, 3H), 6.69 (s, 1H), 2,4-pyrirm ^ indiamine 4.93 (s, 2H), 3.70 (s, 3H), 2.17 (s, 6H); LCMS: purity: 98% MS (m / e): 431 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.75 (s, 1H), 9.53 (s, 1H), N4- [3-Chloro-4-,15 (d, J = 4.5 Hz, 1H), 7.80 (methoxycarbonyl) methyl- (d, J = 2.7 Hz, 1H), 7.66 (dd, 615) enoxyphenyl] -N2- (3.5- J = 2.7 and 9.0 Hz, 1H), 7.00 (d, + + + dimethoxyphenyl) -5-fluoro- J = 9.0 Hz, 1H), 6.81 (d, J = 2, 4-pi? Rimidindian? Ina 2.4 Hz, 1H), 6.14 (t, J = 2.1 Hz, 1H), 4.90 (s, 2H), 3.71 (s, 3H), 3.64 (s, 6H); LCMS: 1 H NMR (DMSO-d 6): d 9.63 (s, 1 H), 9.41 (s, 1 H), N 4 - [3-Chloro-4- 8.12 (d, J = 4.2 Hz, 1 H), 7.76 (methoxycarbonyl) metü- (d, J = 2.7 Hz, 1H), 7.69 (d, 616 enoxyphenyl) -N2- (3-chloro- J = 2.4 Hz, 1H), 7.60 (dd, J = + 4-methoxyphenyl) -5- fluoro- 2.4 and 9.0 Hz, 1H), 7.44 (dd, 2.7 and 8.7 Hz, 1H), 7.04 (d, J = 8.7 Hz, 1H), 7.02 (d, J = 9.0 Hz, 1H), 4.90 (s, 2 H), 1 H NMR (DMSO-d 6): d 9.64 (s, 1 H), 9.45 (s, 1 H), N 2 - (4-Chloro-3,5-8.14 (d, J = 4.2 Hz, 1 H), 7.75 dimetüfeml) -N4- [3- (d, J = 2.4 Hz, 1H), 7.61 (dd, chloro-4-617 J = 2.4 and 9.0 Hz, lH), 7.38 (s, + + + (methoxycarbonyl) methyl- 2H), 7.02 (d, J = 9.0 Hz, 1H), enoxyphenyl] -5-fluoro-2,4- 4.91 (s, 2H), 3.70 (s, 3H), pyrimidinediamine 2.21 (s, 6H); LCMS: purity: 95%; MS (m e): 465 (M +). 1 H NMR (DMSO-d 6): d 10.86 (s, 1 H), 9.23 (s, 1 H), N 4 - [3-Chloro-4- 8.94 (s, 1 H), 8.03 (d, J = 3.9 (methoxycarbonyl) methyl) - Hz, 1H), 7.83 (d, J = 2.4 Hz, 618 enoxyphenyl] -5-fluoro-N2-1H), 7.79 (s, 1H), 7.68 (dd, + (indol-5-yl) -2, 4- J = 2.4 and 9.0 Hz, 1H), 7.25- pyrimidiamine 7.21 (m, 3H), 6.93 (d, J = 9.0 Hz, 1H), 6.27 (t, J = 2.4 Hz, lH), 4.89 (s, 2H), 3.71 (s, 3 1H NMR (DMSO-d6): d 9.63 (bs, 1H), 9.34 (bs, 1H), N4- [3-Chloro-4- (2-8.11 (d, J = 4.2 Hz, 1H), 7.72 droxyethyleneoxy) phenyl] - (d, J = 2.7 Hz, 1H), 7.64 (dd, 619 N2- (3,5-dimethylfenyl) -5- J = 2.7 and 9.0 Hz, lH), 7.12 (d, + fluoro-2,4- J = 8.7 Hz, 1H), 6.58 (s, 1H), p? m ^ mydiamine 4.05 (t, J = 5.1 Hz, 2H), 3.73 (t, J = 5.1 Hz , 2H), 2.16 (s, 6H),; CLEM: purity: 9 No. Compound Name Physical Data Tftase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.29 (s, 1H), 9.13 (s, 1H), N4- [3-Chlorine -4- (2-8.08 (d, J = 3.6 Hz, 1H), 7.75 hydroxyethyleneoxy) phenyl] - (d, J = 2.7 Hz, 1H), 7.71 (dd, 620 N2- (3,5-dimethoxyphenyl) - J = 2.7 and 8.7 Hz, 1H), 7.08 (d, + + 5-fluoro-2,4- J = 9.0 Hz, 1H), 6.90 (d, J = pyrimidinediamine 2.1 Hz, 2H), 6.05 (t, J = 2.1 Hz, 1H), 4.89 (t, J = 5.1 Hz, 1H), 4.05 (t, J = 5.1 Hz, 2H 1H NMR (DMSO-d6): d 9.29 (s, 1H), 9.15 (s, 1H ), N4- [3-Chloro-4- (2- 8.06 (d, J = 3.6 Hz, 1H), 7.74 hydroxyethyleneoxy) feml] - (d, J = 2.1 Hz, 2H), 7.63 (dd, 621 N2- (3-chloro-4- J = 2.7 and 9.0 Hz, 1H), 7.46 methoxyphenyl) -5-fluoro- (dd, J = 2.7 and 9.0 Hz, 1H), 2,4-pyririmidemidomine 7.10 (d, J = 9.0 Hz, 1H), 7.00 (d, J = 9.0 Hz, 1H), 4.87 (t, J = 5.4 Hz, lH), 4.05 (t, J = 5 1H NMR (DMSO-d6): d 9.31 (s) , 1H), 9.18 (s, 1H), N2- (4-Chloro-3,5- 8.08 (d, J = 3.9 Hz, 1H), 7.72 dimethylfenil) -N4- [3- (d, J = 2.7 Hz , 1H), 7.63 (dd, chloro-4- (2-622 J = 2.4 and 9.0 Hz, 1H), 7.42 (s, hid roxyethyleneoxy) phenyl] - + + 2H), 7.12 (d, J = 9.0 Hz, 1H), 5-fluoro-2,4- 4.87 (t, J = 5.7 Hz, 1H), 4.04 pyrimidiamine (t, J = 5.1 Hz, 2H), 3.73 (q, J = 5.1 Hz, 2H), 2.20 (s, 1H NMR (DMSO-d6): d 10.84 (s, 1H), 9.17 (s, 1H), 8.90 (s, 1H) , 8.01 (d, J = 3.9 N4- [3-Chloro-4- (2- Hz, 1H), 7.82-7.76 (m, 2H), hydroxyethyleneoxy) phenyl] -623 7.67 (dd, J = 3.0 and 9.3 Hz , 5-fluoro-N2- (iadol-5-yl) - + + + 1H), 7.25-7.21 (m, 3H), 7.03 2,4-pyrimdd diamir? A (d, J = 9.0 Hz, 1H), 6.28-6.25 (m, 1H), 4.87 (t, J = 5.4 Hz, 1H), 4.04 (t, J = 5.1 Hz, 2H), 1H NMR (DMSO-d6): d 9.49 (s, 1H), 9.42 (s, 1H), N4- [3-Chloro-4- (2-8.12 (d, J = 3.9 Hz, 1H), 7.80 hydroxyethyleneoxy) phenyl] - (d, J = 2.4 Hz, 1H), 7.59 (dd) , 624 N2- (4-chloro-3- J = 2.7 and 9.0 Hz, 1H), 7.40- + + methoxyphenyl) -5-fluoro- 7.36 (m, 1H), 7.30 (dd, J = 2,4-pyrimidindiarnine) 2.7 and 8.4 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.12 (d, J = 8.7 Hz, 1H), 4.06 (t, J = 4.8 Hz, No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3? t IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.84 (s, 1H), 9.20 (s, 1H), 8.91 (s, 1H), 8.02 ( d, J = 3.9 N4- [3-Chloro-4- (N-Hz, 1H), 7.90-7.82 (m, 2H), methyamin) carbonyl- 7.73 (dd, J = 2.4 and 9.0 Hz, 625 methyleneoxyphenyl) - 5-1H), 7.26-7.19 (m, 3H), 6.93 + fluoro-N2- (indol-5-yl) - (d, J = 8.7 Hz, 1H), 6.28 (t, J = 2.4 Hz, 1H) , 4.52 (s, 2H), 2.67 (d, J = 4.5 Hz, 3H); LCMS 1 H NMR (DMSO-d 6): d 2-Chloro-N 4 - (4-chloro-8.17 (d, J = 5.1 Hz, 1H), 7.23 3,5-dimethylphenyl) -5-626 (s, 2H), 3.38 (s, 3H), 2.32 (s, fluoro-N4-methyl-4- + 6H); LCMS: purity: 98%; pyrimidine ina MS (m e): 301 (MH +). 1 H NMR (DMSO-d 6): d 2-Chloro-5-fluoro-N 4 - 7.94 (d, J = 4.8 Hz, 1H), 7.17 methyl-N 4 - [3,4- (d, J = 9.6 Hz, 1H ), 7.17 (d, 627 (tetrafluoroethyl- J = 9.6 Hz, 1H), 7.05-7.00 endioxy) phenyl] -4- (m, 2H), 3.50 (s, 3H); pyriruidinamine CLEM: purity: 92%; MS (m / e): 368 (MH +). 1 H NMR (DMSO-d 6): d 2-Chloro-N 4 - [3,4-7.82 (d, J = 4.5 Hz, 1H), 6.98 (difluoromethyl- (d, J = 8.4 Hz, 1H), 6.90-6.83 628 endioxy) phenyl] -5-fluoro- (m, 2H), 3.40 (s, 3H); N4-methyl-4- LCMS: purity: 100%; Pyrimidinamine EM (m / e): 318 (MH +). 1 H NMR (DMSO-d 6): d 10.86 (s, 1H), 9.67 (s, 1H), 9.14 (s, 1H), 8.44 (dd, J = 2.4 N4- (4-Chloro-3- and 9.0 Hz, 1H), 8.15 (d, J = trifluoromethylphenyl) -5- 3.9 Hz, 1H), 8.12 (d, J = 2.7 629 + fluoro-N2- (indol-6-yl) - Hz, 1H), 7.77 (s, 1H), 7.51 2,4-pyrimidmdiamine (d, J = 9.3 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 2.1 Hz, 1H), 7.14 (dd, J = 1.8 a 1 H NMR (DMSO-d 6): d 10.85 (s, 1 H), 9.35 (s, 1 H), 9.04 (s, 1 H), 8.10 (d, J = 3.6 N 4 - (4-Chloro-3 Hz, 1H), 7.79 (s, 1H), 7.62-methoxyphenyl) -5-fluoro-630 7.57 (m, 2H), 7.36 (d, J = 8.4 + N2- (indol-6-yl) -2.4- + Hz, 1H), 7.24 (d, J = 9.0 Hz, pyirimidinediamine 1H), 7.19 (t, J = 2.7 Hz, 1H), 7.15 (dd, J = 1.8 and 8.4 Hz, 1H), 6.34-6.30 (m, 1H), 3.67 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.78 ( s, 1H), 9.23 (s, 1H), N4- (3-Chloro-4-9.03 (s, 1H), 8.05 (d, J = 3.6 methoxycarbonylmethyl- Hz, 1H), 7.85 (d, J = 2.7 Hz 631 eno xyphenyl) -5-fluoro-N2-1H), 7.79-7.73 (m, 2H), 7.36 + + + (indole-6-yl) -2.4- (d, J = 8.4 Hz, 1H), 7.19 ( dd, pyrimidimediamine J = 2.1 and 8.7 Hz, 1H), 7.16 (t, J = 3.0 Hz, 1H), 6.95 (d, J = 9.0 Hz, 1H), 6.32-6.28 (m, 1H NMR (DMSO-d6) : d 10.79 (s, 1H), 9.19 (d, J = 1.2 Hz, 1H), 9.01 (s, 1H), 8.04 (N4- [3-Chloro-4- (2- d, J = 3.6 Hz, 1 H), 7.84 (d, bydroxyethyleneoxy) phenyl] -632 J = 2.7, 1 H), 7.79-7.73 (, 2 + 5-fluoro-N2- (indol-6-yl) - + H), 7.36 (d, J = 8.4 Hz, 1H), 2,4-pyrimidinediamine 7.19 (dd, J = 1.8 and 8.4 Hz, 1H), 7.16 (t, J = 2.4 Hz, 1H), 7.05 (d, J = 9.3 Hz, 1H) , 1 H NMR (DMSO-d 6): d 9.76 (s, 1 H), 9.63 (s, 1 H), 8.33-8.29 (, 1 H), 8.22 (d, 5-Fluoro-N 2 - [3- (oxazole- J = 3.6 Hz, 1H), 8.16-8.13 2-yl) phenyl] -N4- [3,4- (m, 1H), 7.78-7.74 (m, 1H), 633 (tetrafluoroethyl- 7.62 (dd, J = 2.4 and 9.0 Hz, + endioxy) phenyl] -2,4- 1 H), 7.58-7.53 (m, 1H), pyrimidinediamine 7.42-7.31 (, 3H); LCMS: purity: 92%; MS (m / e): 478 (MH +). 1 H NMR (DMSO-d 6): d 9.67 (s, 1H), 8.57 (t, J = 1.8 5-Fluoro-N 4 -methyl-N 2 -Hz, 1H), 8.18-8.16 (m, 1H), [3- (oxazol-2-yl) phenyl] -8.09 (d, J = 5.7 Hz, 1H), 634 N4- [3,4- (tetrafluoroethyl- 7.72-7.66 (m, 1H), 7.60 (d, + endioxy) phenyl ] -2.4- J = 1.8 Hz, 1H), 7.54-7.47 pyrimidinediamine (m, 2H), 7.39-7.32 (m, 3H), 3.53 (s, 3H); LCMS: purity: 96%; MS (m / e): 492 (MH +). 1 H NMR (DMSO-d 6): d 9.02 (s, 1 H), 8.12-8.06 (m, N 2 - [3,5-Dimethyl-4- (N-1 H), 7.88 (d, J = 5.7 Hz, 1 H) , methyamin) carbonyl- 7.34 (s, 2H), 6.83 (d, J = 6.9 methyneoxyphenyl] -N4- Hz, 1H), 6.82 (s, 1H), 6.73 635 (3, 4-etiiodioxyphenyl) -5- (dd) , J = 3.0 and 9.0 Hz, 1H), + + + fluoro-N4-methyl-2,4- 4.24 (s, 4H), 4.11 (s, 2H), pijrimidmdiamine 3.38 (s, 3H), 2.69 (d, J = 4.8 Hz, 3H), 2.16 (s, 6H); CLEM: pu No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- [ 3,5-Dimethyl-4- (N- 9.15 (s, 1H), 8.12-8.05 (m, methylamino) carboml-1H), 8.02 (d, J = 5.7 Hz, 1H), methyleneoxyphenyl] -5- 8.02 ( d, J = 5.7 Hz, 1H), 7.55 636 fluoro-N4-methyl-N4- (dd, J = 0.9 and 2.7 Hz, 1H), + + [3,4- (tetrafluoro- 7.48 (d, J = 9.3 Hz, 1H), 7.31 ethylendioxy) phenyl] -2,4- (s, 2H), 7.27 (dd, J = 0.9 and 2.1 pmpiidindiamine Hz, 1H), 4.11 (s, 2H), 3.46 (s, 3H), 2.69 (d, J = 4.8 1 H NMR (DMSO-d 6): d N 2 - [3,5-Dimethyl-4- (N- 9.59 (s, 1 H), 9.14 (s, 1 H), methylamino) carbonyl- 8.16- 8.08 (, 3H), 7.61 (dd, methylenexyphenyl) -5- J = 2.7 and 9.0 Hz, 1H), 7.40 (d, 637 fluoro-N4- [3,4- J = 9.0 Hz, 1H), 7.25 (s) , 2H), + (tetrafluoroethyl-4.12 (s, 2H), 2.69 (d, J = 4.8 endioxy) phenyl] -2.4-Hz, 3H), 2.15 (s, 6H); pyridiamine CLEM: purity: 99%; MS (m / e): 526 (MH +). 1 H NMR (DMSO-d 6): d 9.07 (s, 1 H), 8.13-8.05 (m, N 2 - [3,5-Dimethyl-4- (N-1 H), 7.94 (d, J = 5.7 Hz, 1 H) , metaminam) carbonyl- 7.35 (s, 2H), 6.44 (dd, J = 0.6 methyleneoxyphenyl) -N4-638 and 2.4 Hz, 2H), 6.39 (t, J = 2.4 (3, 5-dimethoxyphenyl) -5- + + Hz, 1H), 4.16 (s, 2H), 3.72 fluoro-N4-methyl-2,4- (s, 6H), 3.43 (s, 3H), 2.69 (d, pyriridinediamine J = 4.8 Hz, 3H ), 2.16 (s, 6H); LCMS: purity: 99%; MS 1 H NMR (DMSO-d 6): d 10.60 (s, 1 H), 9.45 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo- 9.09 (s, 1 H), 8.04 (d, J = 3.6 4H-benz [1,4] oxazin-6 Hz, 1H), 7.57 (s, 1H), 7.40-il) -5-fluoro-N2- [1-639 7.33 (m, 2H), 7.31-7.24 (m, (methoxycarbonyl- + 2H), 7.20 (d, J = 3.3 Hz, 1H), methylene) indol-6-yl] -2.4-6.81 (d, J = 8.7 Hz, 1H), 3.35 pyrimidinediamine (d, J = 2.4 Hz, 1H), 4.91 (s, 2H), 3.63 (s, 3H), 1.40 (s, 6H 1H NMR (DMSO-d6): d N4- [3-Chloro-4- (N - 9.42 (s, 1H), 9.24 (s, 1H), methylamino) carbonyl- 8.07 (d, J = 3.9 Hz, 1H), methylenexyphenyl] -5- 7.92-7.84 (m, 2H), 7.71 (dd, 640) fluoro-N2- [l- J = 2.7 and 9.3 Hz, 1H), 7.55 (s, + + (methoxycarbonyl-1H), 7.41 (d, J = 8.4 Hz, 1H), methylene) indol-6-yl] - 2.4- 7.29 (dd, J = 1.5 and 8.4 Hz, pyrimidinediamine 1H), 7.20 (d, J = 3.3 Hz, 1H), 6.94 (d, J = 9.0 Hz, 1H), 6.36 No. Compound Name Data Physic Triptase Triptase Triptase f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.34 (s, 1H), 9.10 (s, 1H) , 8.09 (d, J = 3.6 Hz, 1H), N4- (4-Chloro-3-7.67-7.59 (, 1H), 7.54 (d, methoxyphenyl) -5-fluoro- J = 2.4 Hz, 1H), 7.49 (dd, J = 641 N2- [l- (methoxycarbonyl- + + + 2.4 and 8.4 Hz, 1H), 7.38 (d, J = methylene) indol-6-yl] -2.4- 8.7 Hz, 1H), 7.27-7.22 (m , pyrimidinediamine 2H), 7.20 (d, J = 3.3 Hz, 1H), 6.36 (dd, J = 0.6 and 3.0 Hz, 1H), 1H NMR (DMSO-d6): d 9.19 (s, 1H), 9.14 (s) , 1H), N4- (3.4- 8.02 (d, J = 3.9 Hz, 1H), 7.63 Ethylenedioxyphenyl) -5- (s, 1H), 7.40-7.31 (m, 2H), fluoro-N2- [l - 7.30-7.17 (m, 3H), 6.74 (d, 642 + + (methoxycarbonyl- J = 9.0 Hz, 1H), 6.35 (d, J = methylene) indol-6-yl] -2.4- 2.7 Hz, 1H), 4.90 (s, 2H), pyrimidindiamine 4.21 (s, 4H), 3.63 (s, 3H); LCMS: purity: 93%; MS (m / e): 450 (MH +) 1 H NMR (DMSO-d 6): d 10.56 (s, 1H), 9.20 (s, 1H), N 4 - (2,2-Dimethyl-3-oxo- 8.79 (s) , 1H), 8.00 (d, J = 3.6 4H-benz [1,4] oxazin-6 Hz, 1H), 7.86 (s, 1H), 7.33 il) -5-fluoro-N2- [l- (dd , J = 2.1 and 8.7 Hz, 1H), 643 + (methoxycarbonyl- 7.27-7.16 (m, 4H), 6.83 (d, methylene) indol-5-yl] -2,4- J = 8.7 Hz, 1H), 6.27 (d, J = púim ^ indiamina 3.0 Hz, 1H), 5.05 (s, 2H), 3.66 (s, 3H), 1.40 (s, 6H); LCMS: p 1 H NMR (DMSO-d 6): d 9.22 (s, 1 H), 8.96 (s, 1 H), N 4 - [3-Chloro-4- (N-8.03 (d, J = 3.9 Hz, 1 H), methyamin) carbonyl- 7.90-7.72 (m, 4H), 7.28-7.23 methylenexyphenyl] -5- (m, 3H), 6.94 (d, J = 8.7 Hz, 644 fluoro-N2- [l- + 1H), 6.32 ( d, J = 3.0 Hz, 1H), (methoxycarbonylmethylene) 5.07 (s, 2H), 4.53 (s, 2H), -indol-5-yl] -2.4- 3.67 (s, 3H), 2.67 (d, J = 4.5 pyrmidinediamine Hz, 3H),; LCMS: purity: 90%; MS (m 1 H NMR (DMSO-d 6): d 9.32 (s, 1 H), 8.96 (s, 1 H), N 4 - (4-Chloro-3- 8.07 (d, J = 3.6 Hz, 1 H), 7.84 methoxyphenyl) -5-fluoro- (s, 1H), 7.55-7.47 (m, 2H), 645 N2- [l- (methoxycarbonyl- 7.28-7.17 (m, 4H), 6.29 (d, + methylene) indol-5-yl ] -2.4- J = 3.0 Hz, 1H), 5.08 (s, 2H), pyrimidindiamine 3.67 (s, 3H), 3.64 (s, 3H), CLEM: purity: 96%, MS (m / e): 457 (MH +).

No. Name of Compound Physical Data Tftasa Tffasa Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Tone, 3pt 646 + + 647 + 648 + + + Hz, lH), 4.62 (1H NMR (DMSO-d6): d 9.06 (s, 1H), 9.02 (s, 1H), N4- (3.4-7.99 (d, J = 3.9 Hz, 1H), Ethylenedioxyphenyl ) -5- 7.88-7.82 (m, 1H), 7.58 (s, fluoro-N2- [l- (N- 1H), 7.39-7.33 (m, 2H), 649 methylamin) carbonyl- + + 7.32-7.25 ( m, 2H), 7.16 (d, methyleneindol-6-yl) -2.4- J = 3.3 Hz, 1H), 6.71 (d, J = pyrimidinediamine 8.7 Hz, 1H), 6.33 (d, J = 3.3 Hz, 1H), 4.63 (s, 2H), 4.19 (s, 4H), 2.58 (d 1H NMR (DMSO-d6): d 9.26 (s, 1H), 8.98 (s, 1H), 5-Fluoro-N4- [ 2- (2-hydroxyethyleneoxy) pyrid-5-8.51 (s, 1H), 8.07 (dd, J = 2.4 and 9.0 Hz, lH), 8.03 (d, J = 3.9 il] -N2- [l- (N- 50 Hz, 1H), 7.98-7.92 (m, 1H), methyamin) carbonyl- + methylene-indol-5-yl] -2.4-7.87 (s, 1H), 7.24-7.14 (, 3H), 6.76 (d, J = 9.0 Hz, 1H), pyrimid diamine 6.27 (d, J = 3.0 Hz, 1H), 4.84 (t, J = 5.4 Hz, 1H), 4.72 (No. Compound Name Physical Data Triptase Triptase Tftasa f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1 H NMR (DMSO-d6): d 9.55 (s, 1H), 9.09 (s, 1H), N4- (3-Chloro- 4- 8.15-7.99 (m, 2H), 8.02-7.95 trifluoromethoxyphenyl) -5- (m, 1H), 7.89 (dd, J = 1.5 and fluoro-N2- [l- (N- 9.6 Hz, 1H), 7.75 (s, 1H) , 651 + methyl) carbonyl- 7.40 (d, J = 9.0 Hz, 1H), metiinindol-5-yl] -2.4-7.27-7.21 (m, 3H), 6.30 (d, pyrimidinediamine J = 2.7 Hz, 1H ), 4.73 (s, 2H), 2.61 (d, J = 4.5 Hz, 3H); LCMS: purity 1H NMR (DMSO-dd): d 9.88 (s, 1H), 9.70 (s, 1H), N4- [3-Chloro-4- (N- 8.12-8.03 (m, 2H), 7.94-7.87 methylamin) carboml- (m, 1H), 7.81 (d, J = 2.4 Hz, methyleneoxyphenyl] -5- 1H), 7.69-7.63 (m, 2H), 652 fluoro-N2- [l- (N- + methylamino) carbonyl- 7.35-7.27 (m, 2H), 7.17 (d, J = 8.7 Hz, 1H), 6.94 (d, J = methylene-indol-5-yl] -2.4-9.0 Hz, 1H), 6.35 (d, J = 3.0 pyrimidindiamine Hz, 1H), 4.77 (s, 2H), 4.55 (s, 2H), 2. 1H NMR (DMSO-d6): d 10.22 (s, 1H), 9.91 (s, 1H), N4- (4-Chloro-3- 8.16 (d, J = 4.8 Hz, 1H), methoxyphenyl) -5-fluoro- 8.12-8.05 (m, 1H), 7.70-7.66 N2- [1- (N- (m, 1H ), 7.52-7.48 (, 1H), 653 methylamin) carbonyl- 7.42 (d, J = 7.8 Hz, 1H), + methyleneindol-5-yl] -2,4-737-7.28 (m, 3H), 7.16- 7.10 pyrimidiamine (, 1H), 6.35 (d, J = 2.7 Hz, 1H), 4.79 (s, 2H), 3.63 (s, 3H), 2.62 (d, 1H NMR (DMSO-d6): d 10.21 (s, 1H), 9.94 (s, 1H), N4- (3-Chloro-4- 8.16-8.03 (m, 2H), 7.79-7.74 methoxifeml) -5-fluoro- (m, 1H), 7.65-7.58 (m, 2H), N2- [1- (N- 54 7.37-7.30 (m, 2H), 7.14 (d, methylamin) carbonyl- + J = 8.4 Hz, 1H), 7.05 (d, J = methyleneindol-5-ü] -2.4- 8.7 Hz, 1H), 6.37 (d, J = 3.0 pirin? dindiamine Hz, 1H), 4.78 (s, 2H), 3.84 (s, 3H), 2.61 (d, J = 4.5 Hz, 3H); LC 1 H NMR (DMSO-d 6): d 10.19 (bs, 1H), 10.04 (bs, N 4 - (3,4-1H), 8.12-8.03 (m, 2H), Ethylenedioxyphenyl) -5- 7.66-7.61 (m , 1H), 7.36-7.30 fluoro-N2- [l- (N- (m, 2H), 7.27-7.09 (m, 3H), 55 methylamin) carbonyl- 6.78 (d, J = 8.4 Hz, 1H), 6.38 + methyleneindol-5-yl] -2,4- (d, J = 2.7 Hz, 1H), 4.79 (s, pyrimidineamine 2H), 4.23 (s, 4H), 2.61 (d, J = 4.2 Hz, 3H); LCMS: purity: 99%; EM (No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.46 (s, 1H), 9.07 (s, 1H), N4- [3 -Cloro-4- (N- 8.24-8.17 (m, 1H), 8.11 (d, methyamin) carbonyl- J = 3.0 Hz, 1H), 8.00-7.94 phenyl] -5-fluoro-N2- [l- (, 1H), 7.94-7.86 (m, 2H), 656 + (N-methylamino) carbonyl- 7.77 (s, 1H), 7.31-7.22 (, methyleneindol-5-yl] -2,4- 4H), 6.33 (d , J = 3.3 Hz, 1H), pyrimidindiamine 4.73 (s, 2H), 2.73 (d, J = 4.8 Hz, 3H), 2.60 (d, J = 4.8 Hz, 3H); LC 1 H NMR (DMSO-d 6): d 8.21 (d, J = 3.0 Hz, 1H), 8.15 2-Chloro-5-fluoro-N 4 - (2- (d, J = 5.7 Hz, 1H), 7.78 (dd , 657 methoxypyrid-5-yl) -N4- J = 2.7 and 8.7 Hz, 1H), 6.87 (d, methi-4-pyrMinamine J = 8.7 Hz, 1H), 3.86 (s, 3H), 3.38 (s, 3H ); LCMS: purity: 95%; MS (m / e): 269 (MH +). 1 H NMR (DMSO-d 6): d 2-Chloro-N 4 - (4-chloro-3- 8.25 (d, J = 5.4 Hz, 1 H), trifluoromethyl phenyl) -5- 7.97-7.94 (m, 1H), 7.78- 7.72 658 fluoro-N4-methyl-4- (, 2H), 3.45 (s, 3H); pyrirnidinamine CLEM: purity: 96%; MS (m / e): 341 (MH +). 1 H NMR (DMSO-d 6): d 8.18 (d, J = 5.1 Hz, 1 H), 7.42 2-Chloro-N 4 - (4-chloro-3- (d, J = 8.7 Hz, 1 H), 7.24 (s, methoxyphenyl) -5-fluoro-659 1H), 6.96 (d, J = 8.7 Hz, 1H), N 4 -methyl-4, 3, 82 (s, 1H), 3.31 (s, 3H); piirimidinamine CLEM: purity: 99%; MS (m / e): 303 (MH +). 1 H NMR (DMSO-d 6): d 8.14 (d, J = 5.4 Hz, 1H), 7.56 2-Chloro-N 4 - (3-chloro-4- (d, J = 2.7 Hz, 1H), 7.34 (dd, methoxyphenyl) -5-fluoro- 660 J = 2.4 and 8.7 Hz, lH), 7.15 (d, N4-methyl-4- J = 8.4 Hz, 1H), 3.87 (s, 3H), pyrimidinamine 3.36 (s, 3H); LCMS: purity: 96%; MS (m / e): 303 (MH +). 1 H NMR (DMSO-d 6): d 8.15 (d, J = 5.4 Hz, 1H), 2-Chloro-N 4 - [3-chloro-4- 7.94-7.87 (m, 1H), 7.58 (d, (N- methylamine) carbonyl- J = 2.4 Hz, 1H), 7.32 (dd, J = 61 methyleneoxyphenyl) -5- 2.4 and 8.7 Hz, 1H), 7.02 (d, J = fluoro-N4-methyl-4-9.0 Hz, 1H) ), 4.60 (s, 2H), pyrimidineam 3.36 (s, 3H), 2.66 (d, J = 4.8 Hz, 3H); LCMS: purity: 90%; MS (m / e): 360 (MH +).

No. Name of Compound Physical Data Tftase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.22 (s, 1H) , 9.88 (s, 1H), N4- (3-Chloro-4- 8.22 (d, J = 3.9 Hz, 1H), 8.14 trifluoromethoxyphenyl) -5- (d, J = 2.7 Hz, 1H), 8.02-7.95 fluoro -N2- [l- (N- (, 1H), 7.84-7.78 (m, 1H), 662 methylamin) carbonyl- 7.49 (d, J = 8.1 Hz, 1H), + + methylene-indol-6-yl] -2 , 4-7.47-7.37 (m, 2H), 7.27 (d, pyrimidiamine J = 2.7 Hz, 1H), 7.27 (d, J = 2.7 Hz, 1H), 7.18 (d, J = 8.4 Hz, 1H) 1H NMR (DMSO-dd): d 10.13 (s, 1H), 9.90 (s, 1H), N4- (4-Chloro-3- 8.10 (d, J = 4.5 Hz, 1H), 7.91 methoxyphenyl) -5-fluoro- (d, J = 3.9 Hz, 1H), 7.49-7.34 N2- [1- (N- 663 (m, 4H), 7.23 (d, J = 3.3 Hz, methyamin) carbonyl- + 1H), 7.17 (d, J = 8.4 Hz, 1H), methyleneindol-6-yl] -2.4-7.07 (d, J = 8.4 Hz, 1H), 6.37 pyrimidinediamine (d, J = 3.0 Hz, 1H), 4.62 (s, 2H) , 3.52 (s, 3H), 2.51 (d, 1H NMR (DMSO-d6): d 10.21 (s, 1H), 10.04 (s, 1H), N4- (3-Chloro-4- 8.14 (d, J = 5.1 Hz, 1H), methoxyphenyl) -5-fluoro- 7.98-7.92 (m, 1H), 7.84 (d, N2- [1- (N- J = 2.7 Hz, 1H), 7.60 (dd, J = 664 + + methyamin) carbonyl- 2.4 and 8.7 Hz, 1H), 7.51 (d, J = methylene-indol-6-yl) -2.4- 8.7 Hz, 1H), 7.39 (s, 1H), pyrimidinediamine 7.30 (d, J = 3.3 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 7.01 (d, J = 1H NMR (DMSO-d6): d 9.50 (s, 1H), 9.19 (s, 1H), N4- [3-Chloro-4- (N- 8.28-8.20 (m, 1H), 8.12 (d, methylamino) carbonyl- J = 3.3 Hz, 1H), 7.97-7.84 phenyl] -5-fluoro-N2- [l- (m, 3H), 7.53 (s, 1H), 7.42.665 + (N-methyamin) carbonyl- (d, J = 8.7 Hz, 1H), 7.32-7.25 metüenindol-6-yl] -2.4- (d, J = 3.3 Hz, 1H ), 6.35 (d, pyrinridindiamine J = 3.0 Hz, 1H), 4.63 (s, 2H), 2.74 (d, J = 4.5 Hz, 3H), 2.58 (d, J 1H NMR (DMSO-d6): d 9.94 ( s, 1H), 8.28 (dd, J = 0.6 and 3.6 Hz, 1H), 7.75 (d, J = 2.1 2-Chloro-N4- (3-chloro-4-Hz, 1H), 7.58 (dd, J = 2.4 and 66 methoxypheni) -5-fluoro-4- 8.7 Hz, 1H), 7.16 (d, J = 8.7 pyrimdinamine Hz, 1H), 3.84 (s, 3H); LCMS: purity: 96%; MS (m / e): 288 (M +).

No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.38 (s, 1H) , 9.28 (s, 1H), 8.28 (s, 1H), 8.14-8.10 (m, 5-Fluoro-N2- [3- (oxazole-2H), 7.87 (d, J = 7.2 Hz, 1H), 2- il) phenyl] -N 4 - (3,4,5-667 7.50 (d, J = 7.5 Hz, 1H), + trimethoxyphenyl) -2,4-734-7.27 (m, 2H), 7.06 (s, pyrimidinediamine 2H) ), 3.70 (s, 6H), 3.63 (s, 3H); LCMS: purity: 98%; MS (m / e): 438 (MH +). 1 H NMR (DMSO-d 6): d 9.10 (s, 1 H), 7.96 (d, J = 3.9 Hz, 1 H), 7.75 (s, 1 H), 7.50 N 4 - (3,4- (d, J = 8.7 Hz , 1H), 7.26 (d, Ethylenedioxyphenyl) -5- J = 2.4 Hz, 1H), 7.10 (dd, J = 668 fluoro-N2- (2,3,4- + 2.4 Hz, 1H), 6.74-6.64 ( m, trimethoxyphenyl) -2,4-2H), 4.25-4.18 (, 4H), 3.77 pyrimidiamine (s, 3H), 3.75 (s, 3H), 3.74 (s, 3H); LCMS: purity: 99%; MS (m / 1 H NMR (DMSO-d 6): d 9.26 (s, 1 H), 8.01 (d, J = 3.6 N 4 - (3-Chloro-4 Hz, 1 H), 7.86 (s, 1 H), 7.81 methoxyphenyl ) -5-fluoro- (d, J = 2.7 Hz, 1H), 7.54 (dd, 669 N2- (2,3,4- J = 2.4 and 9.0 Hz, 1H), 7.43 (d, trimethoxyphenyl) -2, 4- J = 9.0 Hz, 1H), 7.03 (d, J = pyrirrindindiamine 9.0 Hz, 1H), 6.70 (d, J = 9.3 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 3.74 (s, 3H), 3.73 1H NMR (DMSO-dd): d 816 (d, J = 4.8 Hz, 1H), 7.56- N4- (4-Chloro-3-7.51 (m, 1H), 7.36-7.24 ( m, methoxyfenu) -5-fluoro-4H), 6.74 (d, J = 9.3 Hz, 1H), 670 N2- (2,3,4-3.80 (s, 3H), 3.74 (s, 3H), trimethoxyphenyl) -2.4- 3.73 (s, 3H), 3.68 (s, 3H), pyrimidinediamine LCMS: purity: 95%, MS (m / e): 436 (MH +). 1H NMR (DMSO-d6): d 8.20 (d, J = 4.5 Hz, 1H), 8.05 N4- (3-Chloro-4- (d, J = 2.7 Hz, 1H), 7.73-7.66 trifluoro-aethoxyphenyl) -5- (m, 1H), 7.45 (d, J = 9.6 Hz, 671 fluoro-N2- (2,3,4-1H), 7.24 (d, J = 8.7 Hz, 1H), + trimethoxyphenyl) -2.4-6.75 (d, J = 9.0 Hz, 1H), 3.78 pyrimidinediamine (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), CLEM: purity: 95%; MS (m / e): 490 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 672 673 + + 674 + + 675 + + 76 + No. Name of Compound Physical Data Tftasa Triptasa Tftasa f syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d Salt of acid 2,4,6- 11.10 (s, 1H), 9.72 ( s, 1H), trimethylbenzenesulfonic 9.47 (s, 1H), 8.15 (d, J = 4.2 of N4- (2,2-Dimethyl-3- Hz, 1H), 7.62-7.56 (m, 1H), oxo-4H- 5-677 7.31 (d, J = 8.1 Hz, 1H), 6.91 pyrid [1, 4] oxazin-6-yl) -5- (s, 2H), 6.72 (s, 2H), 3.66 (s, fluoro- N2- (3.4.5-6H), 3.61 (s, 3H), 2.48 (s, trimethoxyphenyl) -2,4-6H), 2.16 (s, 3H), 1.43 (s, pyrimidinediamine 6H). 1 H NMR (DMSO-d 6): d 11.08 (s, 2H), 9.46 (s, 2H), Pyridin-3-9.30 (s, 2H), 8.91 (s, 1H), sulfonic acid salt of N4- (2H). , 2- 8.70 (d, J = 5.4 Hz, 1H), 8.37 Dimethyl-3-oxo-4H-5- (dd, J = 1.5 and 7.8 Hz, 1H), 678 pyrid [1,4] oxazin-6 il) -5- 8.13 (d, J = 3.6 Hz, 2H), + + fluoro-N2- (3,4,5-trimethoxyphenyl) -2.4- 7.80-7.74 (m, 1H), 7.62 (d, J = 8.1 Hz, 2H), 7.31 (d, J = pyrimidindiamine 0.5 8.1 Hz, 2H), 6.97 (s, 4H), 3.66 (s, 1 1 H NMR (DMSO-dd): d Salt of the acid p- 11.08 ( s, 1H), 9.44 (s, 1H), ethylbenzenesulfonic of 9.26 (s, 1H), 8.13 (d, J = 3.3 N4- (2,2-Dimethyl-3-oxo-Hz, 1H), 7.63 (d, J = 8.4 Hz, 679 4H-5-pyrid [1,4] oxazin-1H), 7.47 (d, J = 8.1 Hz, 2H), + 6-yl) -5-fluoro-N2- (3,4, 5- 7.31 (d, J = 8.1 Hz, 1H), 7.12 trimethoxyphenyl) -2.4- (d, J = 7.8 Hz, 2H), 6.97 (s, pyripindinediamine 2H), 3.65 (s, 6H), 3.59 ( s, 3H), 2.57 (q, J = 7.8 Hz, 2H), 1H NMR (DMSO-d6): d Salt of acid 1.2-11.08 (s, 2H), 9.54 (s, 2H), ethanedisulfonic acid of N4 - (2,2-Dimethyl-3-oxo-4H- 9.35 (s, 2H), 8.14 (d, J = 3.9 Hz, 2H), 7.60 (d, J = 8.4 Hz, 680 5-pyrid [1,4] oxazin-6-yl) -2H), 7.31 (d, J = 8.4 Hz, 2H), + 5-fluoro- N2- (3.4.5-6.95 (s, 4H), 3.66 (s, 12H), trimethoxyphenyl) -2.4- 3.60 (s, 6H), 2.62 (s, 4H), pyrimidinediamine 0.5 1.43 (s, 12H). 1 H NMR (DMSO-d 6): d Salt of the acid (1R) -10-11.11 (s, 1H), 9.83 (s, 1H), camphorsulfonic of N4-9.54 (s, 1H), 8.17 (d, J = 3.9 (2,2-Dimethyl-3-oxo-4H-Hz, 1H), 7.57 (d, J = 8.7 Hz, 81 5-pyrid [1,4] oxazin-6-yl) - 1H), 7.30 (d, J = 8.4 Hz, 1H), 5-fluoro-N2- (3.4.5-6.99 (s, 2H), 3.66 (s, 6H), trimethoxyphenyl) -2.4-3.61 (s, 3H), 2.86 (d, J = 14.7 p? imdmdiamine Hz, 1H), 2.67 (t, J = 9.9 Hz, 1H), 2.38 (d, J = 14.7 Hz, 1H) No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1 H NMR (DMSO-d6): d 11.08 (s, 1H), 9.55 (s, 1H), Salt of the acid (1S) ) -10- 9.36 (s, 1H), 8.14 (d, J = 3.9 camphorsulfonic of N4-Hz, 1H), 7.60 (d, J = 8.7 Hz, (2,2-Dimethyl-3-oxo-4H-1H) ), 7.31 (d, J = 8.4 Hz, 1H), 682 5-pyrid [1,4] oxazin-6-yl) -6.94 (s, 2H), 3.66 (s, 6H), + + 5-fluoro- N2- (3.4.5- 3.60 (s, 3H), 2.85 (d, J = 14.7 trimethoxyphenyl) -2.4-Hz, 1H), 2.68 (t, 11.4 Hz, pyrimidinediamine 1H), 2.36 (d, J = 14.7 Hz, 1H), 1H NMR ( DMSO-d6): d 11.04 (s, 1H), 9.08-8.90 (, N4- (2,2-Dimethyl-3-oxo-2H), 8.07 (d, J = 3.3 Hz, 1H), 4H-5- pyrid [1,4] oxazin- 7.99-7.89 (m, 1H), 7.81-7.96 6-yl) -5-fluoro-N2- [l- (N- (m, 1H), 7.70-7.64 (m, 1H ), 683 + methylamino) carbonyl- + 7.29-7.20 (m, 4H), 6.29 (d, methyleneindol-5-yl] -2.4- J = 3.0 Hz, 1H), 4.73 (s, 2H), pyrimidinediamine 2.61 (d, J = 4.5 Hz, 3H), 1.42 (s, 6H),; LCMS: purity: 99%; Salt of p-1H NMR acid (DMSO-d6): d-toluenesulfonic acid of N2-11.13 (s, 1H), 9.68 (s, 1H), (4-Chloro-3,5-9.46 (s, 1H), 8.17 ( d, J = 3.6 dimethylphenyl) -N4- (2.2-684 Hz, 1H), 7.51-7.35 (, 6H), + dimethyl-3-oxo-4H-5-7.90 (d, J = 8.4 Hz, 2H ), 2.28 pyrid [1,4] oxazin-6-yl) -5- (s, 3H), 2.22 (s, 6H), 1.43 (s, fluoro-2,4- 6H). pyrimidinediamine 1 H NMR chloride salt (DMSO-d6): d N4- hydrogen (2.2- 11.31 (s, 1H), 9.89 (s, 1H), Dimethyl-3-oxo-4H-5-9.66 (s) , 1H), 8.18 (d, J = 4.5 685 pyrid [1,4] oxazin-6-yl) -5-Hz, 1H), 7.55 (d, J = 8.4 Hz, + fluoro-N2- (3.4 , 5-1H), 7.30 (d, J = 8.7 Hz, 1H), trimethoxyphenyl) -2.4-6.89 (s, 2H), 3.65 (s, 6H), pñ-inñdmdiamine 3.61 (s, 3H), 1.43 (s, 6H) 1 H NMR (DMSO- <6): d 11.07 (s, 1H), 9.32 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.27 (s, 1H) , 8.13 (d, J = 3.3 4H-5-? Irid [1,4] oxazin-Hz, 1H), 7.63 (s, 2H), 7.45 86 6-yl) -N2- (3,5-dichloro-4) - (d, J = 8.7 Hz, 1H), 7.35 (d, hydroxyphenyl) -5-fluoro- J = 8.7 Hz, 1H), 1.43 (s, 6H); 2,4-pyrimidinediamine LCMS: purity: 92%; MS (m / e): 467 (MH +).

No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt N2, N4-Bis (3-oxo-2,2,4-trimethyl-5- 687 pyrid [1,4] oxazin-6-yl) -5- + fluoro-2,4-pmmidmdiamine N2, N4-Bis (2,2-dimethyl-4-carbomethoxymethyl-3- 688 oxo-5-pyrid [1,4] oxazin-6-yl) -2,4-pyrimidinediamine -Fluoro-N 4 - (3-oxo-2,2,4-trimethyl-5-pyrid [1,4] oxazin-6-yl) -689 N 2 - (3,4,5-trimethoxyphenyl) -2,4 - piriimtimdiainina N 4 - (2,2-Dimethyl-4-carbomethoxymethyl-3-oxo-5-pyrid [1,4] oxazin-690 + 6-yl) -5-fluoro-N 2 - (3,4,5-trimethoxyphenyl) - 2,4- pir ^ dindiamine N4- (2,2-Dimethyl-4-carbomethoxymethyl-3-1H), 6.98 (s, 2H), 6.81 (dd, oxo-5-pyrid [1,4] oxazin- J = 3.3 and 8.4 Hz, 1H) , 4.83 (s, 691 6-yl) -5-fluoro-N4- + 2H), 4.63 (s, 2H), 3.72 (s, carbomethoxymethyl-N2-6H), 3.63 (s, 3H), 3.59 (s, (3,4,5-trimethoxyphenyl) -3H), 3.57 (s, 3H), 1.47 (s, 2,4-pyrimidinediamine 6H); LCMS: purity: 99%; MS (m No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSCW6): d N2- [3, 5-Dimethoxy-4- (2-11.04 (s, 1H), 9.14 (s, 1H), (N- 9.09 (s, 1H), 8.11 (d, J = 3.6 morpholin) ethyloxy) phenyl] - Hz, 1H ), 7.65 (d, J = 8.4 Hz, 692 N4- (2,2-dimethyl-3-oxo-1H), 7.31 (d, J = 8.4 Hz, 1H), + + 4H-5-pyrid [1, 4] oxazin- 7..02 (s, 2H), 3.87 (t, J = 6.0 6-yl) -5-fluoro-2,4-Hz, 2H), 3.65 (s, 6H), 3.58- pyrimidinediamine 3.53 (m, 4H), 2.58 (t, J = 6.0 Hz, 2H), 2.47-2.42 (m, 4H), 1H NMR (DMSO-d6): d 11.07 (s, 1H), 10.91 (s, 1H), 9.27 (s, 1H), 9.12 (s, 1H), N2, N4-Bis (2,2-dimethyl-8.13 (d, J = 3.3 Hz, 1H), 7.69 3-oxo-4H-5- (d, J = 8.4 Hz, 1H), 7.60 (d, 693 pyrid [1,4] oxazin-6-yl) -5- + J = 9.0 Hz, 1H), 7.32 (d, J = fluoro-2,4- 8.4 Hz, 1H), 7.22 (d, J = 9.0 piíip? Dindiamina Hz, 1H), 1.43 (s, gH), 1.39 (s, 6H), CLEM: purity: 99%, MS 1H NMR (DMSO-d6): d 10.36 (s, 1H), 10.21 (s, 1H), 8.24 (d, 1H, J = 4.9 Hz), 7.92 (s, 1H), 7.83 (s, 1H), 7.74 (d, 1H, J = 2.6 Hz), 7.65 (d, 1H, N4- (3-Chloro-4- J = 9.1 Hz), 7.54 (app dd) , methoxyphenyl) -N2- (l- 1H, J = 2.3 and 9.1 Hz), 7.38 694 ethylindazol-5-yl) -5- (dd, 1H, J = 1.8 and 9.1 Hz), + + fluoro-2,4 - 7.09 (d, lH, J = 9.1 Hz), 4.40 pyrimidinediamine (qt, 2H, J = 7.0 Hz), 3.83 (s, 3H), 1.38 (t, 3H, J = 7.0 Hz). CLEM: time ret: 9.30 ruin; purity: 97%; MS (m / e): 414 (MH +) T NMR (DMSO-d6): d 10.28 (s, 1H), 10.02 (s, 1H), 8.28 (d, N4- (3,4-Dichlorofenu) -1H, J = 4.7 Hz), 8.02 (d, 1H, J = N2- (1-ethylindazol-5-yl) -2.3 Hz), 7.94 (s, 1H), 7.87 (s, 695 5-fluoro-2,4- 1H), 7.70 (s, 1H), 7.66 (d, 1H, J pyrimidinediamine = 9.1 Hz), 7.52 (d, 1H, J = 8.8 Hz), 7.42 (dd, 1H, J = 2.3 and 8.8 Hz), 4.41 (qt, 2H, J = 7.0 Hz T NMR pMSO-d6): d 10.77 (s, 1H), 10.39 (s, 1H), 10.21 (s, N4- (2,2-Dimethyl-3-oxo- 1H) , 8.22 (d, 1H, J = 5.3 Hz), 4H-benz [1,4] oxazin-6- 7.89 (s, 2H), 7.61 (d, lH, J = 8.8 696 ü) -N2- (l- ethylindazole-5- + + Hz), 7.37 (d, 1H, J = 8.8 Hz), ü) -5-fluoro-2,4-7-20 (dd, 2H, J = 2.3 and 8.2 Hz), pyrimidinediamine 6.81 (d , 1H, J = 8.2 Hz), 4.39 (qt, 2H, J = 7.0Hz), 1.37 (s, 6 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 10.42 (s, 1H), 10.29 (s, 1H), 8.26 (d, 1H, J = 4.9 Hz), 7.89 N2- ( 1-Ethylindazol-5-yl) - (s, 2H), 7. 63 (d, 1H, J = 8.8 5-fluoro-N4- (4-f? Uoro-3-694 Hz), 7.44 (d, 1H, J = 8.2 Hz), methoxyphenyl) -2.4-7.37 (d , 1H, J = 9.0 Hz), pninndindiamine 7.31-7.23 (m, 1H), 7.19 (dd, 1H, J = 8.8 and 11.8 Hz), 4.41 (qt, 2H, J = 7.0 Hz), 3.60 JH NMR (DMSO -d6): d 10.44 (s, 1H), 10.40 (s, 1H), N4- (3-Chloro-4- 8.32 (d, 1H, J = 4.9 Hz), 7.92 methoxyphenyl) -N2- (l- ( s, 1H), 7.78 (app t, 2H, J = 698 ethylindazol-6-yl) -5- 2.6 Hz), 7.67 (d, 1H, J = 8.5 + + fluoro-2,4-Hz), 7.58- 7.52 (dt, 1H, J = pyrimidinediamine 2.6 and 9.1 Hz), 7.16 (d, 1H, J = 8.8 Hz), 7.10 (d, 1H, J = 9.1 Hz), 4.11 (qt, 2H, J! H NMR ( DMSO-d6): d 9.92 (s, 1H), 9.78 (s, 1H), 8.27 (d, 1H, J = 4.1 HzO, 8.08 (app d, N4- (3,4-dichlorophenyl) - 1H, J = 2.6 Hz), 7.93 (s, 1H), N2- (l-etyindazol-6-yl) -699 7.91 (s, lH), 7.76 (dt, 1H, J = + 5-fluoro-2,4 - + 2.6 and 8.1 Hz), 7.62 (d, 1H, J pu-imidyndiamine = 8.5 Hz), 7.54 (d, 1H, J = 8.8 Hz), 7.23 (d, 1H, J = 8.5 Hz), 4.14 (qt , 2 * H NMR (DMSO-d6): d 10.75 (s, 1H), 10.18 (s, 2H), 8.25 (d, 1H, J = 4.7 Hz), 7.94 N4- (2,2-Dimethyl-3-) oxo- (s, 1H), 7.84 (s, 1H), 7.63 (d, 4H-benz [1,4] oxazin-6- 1H, J = 8.5 Hz), 7.27-7.17 700 il) -N2- (l ethylindazole-6- + (m, 3H), 6.86 (d, 1H, J = 8.5 il) -5-fluoro-2,4-Hz), 4.14 (qt, 2H, J = 7.0 pyrimidinediamine Hz), 1.38 ( s, 6H), 1.28 (t, 3H, J = 7.0 Hz), CLEM: t ret.H NMR (DMSO-d6): d 10.18 (s, 2H), 8.26 (d, 1H, J = 4.7 Hz), 7.93 (s, 1H), 7.90 N2- (1-Ethylindazol-6-yl) - (s, 1H), 7.62 (d, 1H, J = 8.5 5-fluoro-N4- (4-fluoro- 3- Hz), 7.50-7.46 (m, 1H), 701 methoxyphenyl) -2.4- + 7.30-7.27 (m, 1H), 7.19-7.13 pyrimidindiamine (m, 2H), 4.09 (qt, 2H, J = 7.0 Hz), 3.60 (s, 3H), 1.27 (t, 3H, J = 7.0 Hz) CLEM: time ret.

No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3? T] H NMR (DMSO-d6): d 10.39 (s , 1H), 10.26 (s, 1H), N4- (3-Chloro-4- 8.26 (d, 1H, J = 4.7 Hz), 7.92 methoxyphenyl) -5-fluoro- (s, 1H), 7.82 (s, 1H), 7.75 (d, 702 N2- (l-«- propylindazole-1H, J = 2.7 Hz), 6.66 (d, 1H, + 5-il) -2.4- J = 9.1 Hz), 7.54 (dt , 1H, J = pyrimidmdiamine 2.3 and 9.1 Hz), 7.08 (d, 1H, J = 9.1 Hz), 4.33 (t, 2H, J = 7.0 Hz), 3.83 (s, 3H) 'H NMR (DMSO-d6) : d 10.21 (s, 1H), 9.93 (s, 1H), 8.26 (d, 1H, J = 4.4 Hz), 8.01 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.6 Hz ), 7.94 (s, fluoro-N2- (l- «-703 1H), 7.87 (s, 1H), 7.69 (dd, +? Ropilindazol-5-yl) -2,4- 1H, J = 1.8 and 8.8 Hz), 7.65 pyrmidinediamine (d, 1H, J = 9.1 Hz), 7.49 (d, 1H, J = 8.8 Hz), 7.41 (dd, 1H, J = 9.1 Hz), 4.34 (t, 2H, 'H NMR ( DMSO-dd): d 10.75 (s, 1H), 10.21 (s, 2H), N4- (2,2-Dimethyl-3-oxo- 8.26 (d, 1H, J = 4.9 Hz), 7.94 4H-benz [ l, 4] oxazin-6- (s, 1H), 7.83 (s, 1H) 7.63 (d, 704 il) -5-fluoro-N2- (ln-1H, J = 8.8 Hz), 7.27-7.17 + propylindazol-5-yl) -2.4- (m, 3H), 6.86 (d , 1H, J = 8.8 pyrimidinediamine Hz), 4.06 (t, 2H, J = 7.0 Hz), 1.72 (qt, 2H, J = 7.0 Hz), 1.38 (s, 6H), 0.71 (t, 3H, lH NMR ( DMSO-d6): d 10.46 (s, 1H), 10.35 (s, 1H), 8.28 (d, 1H, J = 4.9 Hz), 7.90 5-Fluoro-N4- (4-fluoro- (s, I H) , 7.87 (s, 1H), 7.63 (d, 3-methoxyphenyl) -N2- (l- «- 705 1H, J = 9.1 Hz), 7.43 (dd, propylindazol-5-yl) -2,4- + 1H , J = 2.3 and 8.8 Hz), 7.27- pyrimidiamine 7.22 (m, 1H), 7.14 (dd, 1H, J = 1.8 and 1 Hz), 4.34 (t, 2H, J = 7.0 Hz), 3.60 (s,! H NMR (DMSO-d6): d 10.51 (s, 1H), 10.44 (s, 1H), N4- (3-Chloro-4-3.33 (d, 1H, J = 4.9 Hz), 7.96 methoxyphenyl) -5- fluoro- (s, 1H), 7.77 (d, 1H, J = 2.6 706 N2- (l - «-? ropilindazol- Hz), 7.67 (d, lH, J = 8.8 Hz), + 6-il) -2 , 4- 7.55 (dd, 1H, J = 2.6 and 8.8 pyrimidinediamine Hz), 7.16 (dd, 1H, J = 2.6 and 8.8 Hz), 4.03 (t, 2H, J = 7.0 Hz), 3.83 (s, 3H) , 1.6 No. Compound Name Physical Data Triptase Triptase Tftasa f_syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt ¡H NMR (DMSO-d6): d 10.15 (s, 1H), 10.02 (s, 1H), 8.30 (d, 1H, J = 4.4 Hz), 8.06 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.6 Hz), 7.93 (s, fluoro-N2- (l- «- 707 1H ), 7.89 (s, 1H), 7.73 (dd, propylindazol-6-yl) -2.4- 1H, J = 2.6 and 8.5 Hz), 7.65 pyrimidinediamine (d, 1H, J = 8.5 Hz), 7.55 (d) , 1H, J = 8.8 Hz), 7.21 (d, lH, J = 8.8 Hz), 4.07 (t, 2H,! H NMR (DMSO-dd): d 10.77 (s, 1H), 10.37 (s, 1H) , N4- (2,2-Dimethyl-3-oxo-10.16 (s, 1H), 8.21 (d, 1H, J 4H-benz [1,4] oxazin-6- = 5.3 Hz), 7.89 (s, 1H ), 7.87 708 il) -5-fluoro-N2- (l - «- (s, 1H), 7.61 (d, 1H, J = 8.8 propylindazol-6-yl) -2.4-Hz), 7.37 (dd) , 1H, J = 1.8 and pyriridinediamine 8.8 Hz), 7.20 (d, 1H, J = 8.8 Hz), 8.87 (d, lH, J = 8.8 Hz), 4.31 (t, 2H, J = 7.0 Hz) 'H NMR (DMSO-d6): d 10.40 (s, 1H), 10.37 (s, 1H), 8.33 (d, lH, J = 5.0 Hz), 7.96 5-Fluoro-N4- (4-fluoro- (s, 1H) , 7.84 (s, 1H), 7.64 (d, 3-methoxyphenyl) -N2- (l- «-709 1H, J = 8.5 Hz), 7 .47 (dt, 1H, propylindazol-6-yl) -2,4- J = 1.8 and 8.5 Hz), 7.26-7.22 pyrimidinediamine (m, 2H), 7.15 (dd, 1H, J = 11.8 and 8.8 Hz), 4.02 (t, 2H, J = 7.0 Hz), 3.55 (s, lH NMR (DMSO-d6): d 10.40 (s, 1H), 10.27 (s, 1H), 7.92 (s, 1H), 7.82 (s, 1H), N2- (l- «- Butylindazole-5-7.75 (d, 1H, J = 2.3 Hz), 7.65 il) -N4- (3-chloro-4-710 (d, 1H, J = 9.1 Hz) , 7.54 (dd, methoxyphenyl) -5-fluoro- 1H, J »2.3 and 9.1 Hz), 7.39 2,4-pyrimidinediamine (d, 1H, J = 9.1 Hz), 7.09 (d, 1H, J = 9.1 Hz) , 4.36 (t, 2H, J = 7.3 Hz), 3.83 (s, 3H) * H NMR (DMSO-dd): d 10.43 (s, 1H), 10.20 (s, 1H), 8.32 (d, 1H, J = 4.7 Hz), 8.00 N2- (ln-Butylindazole-5- (d, 1H, J = 2.3 Hz), 7.95 (s, il) -N4- (3.4-711 1H), 7.83 (s, 1H) , 7.67 (d, dichlorophenyl) -5-fluoro-2H, J = 8.8 Hz), 7.49 (d, 1H, 2,4-pyrimidinediamine J = 8.8 Hz), 7.41 (dd, 1H, J = 2.3 and 8.8 Hz) , 4.38 (t, 2H, J = 7.3 Hz), 1.79 (q, 2H, No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE,8pt Ion, 3pt 'H NMR (DMSO-d6): d 10.75 (s), 1H), 10.28 (s, 1H), N2- (lH-Butylindazole-5-10.05 (s, 1H), 8.19 (d, 1H, J il) -N4- (2,2-dimethyl-3- = 4.9 Hz), 7.89 (s, 2H), 7.60 oxo-4H-712 (d, 1H, J = 9.1 Hz), 7.38 (d, benz [1,4] oxazin-6-yl) -5- + 1H , J = 9.1 Hz), 7.20 (dd, fluoro-2,4- 1H, J = 1.8 and 9.1 Hz), 7.16 pyrimidinediamine (s, 1H), 6.86 (d, 1H, J = 9.1 Hz), 4.35 (t , 2H, J = 7.3 Hz) * H NMR (DMSO-d6): d 10.42 (s, 1H), 10.29 (s, 1H), 8.27 (d, 1H, J = 4.9 Hz), 7.89 N2- (l- «-Butinindazole-5- (s, 1H), 7.87 (s, 1H), 7.63 (d, ü) -5-fluoro-N4- (4-713 1H, J = 8.8 Hz), 7.43 (dd, + + fluoro-3-methoxyphenyl) - 1H, J = 2.3 and 8.8 Hz), 7.36 2,4-pyrimidinediamine (dd, 1H, J = 1.8 and 9.1 Hz), 7.28-7.23 (m, 1H), 7.13 (dd, lH , J = 11.3 and 9.1 Hz0, lH NMR (DMSO-d6): d 10.27 (s, 2H), 8.30 (d, 1H, J = 4.7 Hz), 7.94 (s, 1H), 7.82 N2- (l-; -Butinindazole-6- (s, 1H), 7.77 (d, 1H, J = 2.6 il) -N4- (3-chloro-4-Hz), 7.65 (d, lH, J = 8.8 Hz), 714 + methoxyphenyl ) -5-fluoro- 7.56 (dd, 1H, J = 2.6 and 8.8 2,4-pyrrho-dindiamine Hz), 7.16 (d, 1H, J = 8.8 HzO, 7.11 (d, 1H, J = 8.8 Hz), 4.06 (t, 2H, J = 7.3 Hz), 3? H NMR (DMSO-d6): d 10.21 (s, 1H), 10.09 (s, 1H), 8.32 (d, 1H, J = 4.4 Hz), 8.05 N2- (l - «- Butylindazole-6- (d, 1H, J = 2.3 Hz), 7.94 (s, il) -N4- (3, 4-715 1H), 7.86 (s, 1H0, 7.72 (d, dichlorophenyl) -5-fluoro-1H, J = 8.8 Hz), 7.66 (d, 1H, 2,4-pyrimidinediamine J = 8.8 Hz), 7.55 ( d, 1H, J = 8.8 Hz), 7.20 (d, 1H, J = 8.8 Hz), 4.11 (t, 2H, J = 7.3 lH NMR (DMSO-d6): d 11.77 (s, 1H), 10.40 (s) , 1H), N2- (l-? - Butylindazole-6- 10.36 (s, 1H), 8.29 (d, 1H, J ü) -N4- (2,2-dimethyl-3- = 4.9 Hz), 7.94 ( s, 1H), 7.81 oxo-4H-716 (s, 1H), 7.62 (d, 1H, J = 8.8 benz [1,4] oxazin-6-yl) -5-Hz), 7.23 (s, 2H) , 7.18 (d, fluoro-2,4- 1H, J = 8.8 Hz), 6.85 (d, 1H, pyriridinediamine J = 8.8 Hz), 4.10 (t, 2H, J = 7.3 Hz), 1.67 (q, 2H, J = 7 No. Compound Name Physical Data Triptase Tftase Tftasa F syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt! H NMR (DMSO-d6): d 10.42 ( s, 1H), 10.37 (s, 1H), 8.33 (d, 1H, J = 4.7 Hz), 7.96 N2- (l- «- Butylindazole-6- (s, 1H), 7.84 (s, 1H), 7.64 (d, il) -5-fluoro-N4- (4-717 1H, J = 8.8Hz), 7.50-7.46 fluoro-3-methoxyphenyl) - + (, 1H), 7.27-7.22 (, 1H), 2,4-? Irimidindiamine 7.16 (app t, 1H, J = 11.8 and 8.8 Hz), 4.06 (t, 2H, J = 7.3 Hz), 3.54 (s, 3H), 1.65 (q, >; H NMR (DMSO-d6): d 10.19 (s, 1H), 10.03 (s, 1H), N4- (3-Chloro-4- 8.22 (d, 1H, J = 4.9 Hz), 7.90 methoxyphenyl) -N2 - [l- (s, 1H), 7.84 (s, 1H), 7.76 (d, 718 (cyclohexylmethyl) indazole-1H, J = 2.6 Hz), 7.62 (d, 1H, + 5-yl] -5-fluoro -2.4- J = 9.1 Hz), 7.56 (dd, 1H, J = 2.6 and 9.1 Hz), 7.39 (dd, 1H, J = 1.8 and 9.1 Hz), 7.09 (d, 1H, J = 9.1 Hz) , 4.2 T NMR (DMSO-d6): d 9.69 (s, 1H), 9.38 (s, 1H), 8.17 (d, N2- [l- 1H, J = 3.8 Hz), 8.07 (app d, (Cyclohexylmethyl) indazole 1H, J = 2.6 Hz), 7.92 (s, 1H), 719 -5-yl] -N4- (3.4-7.88 (s, lH0, 7.78 (d, 1H, J = + dichlorophenyl) -5- fluoro- 8.8 Hz), 7.58 (d, 1H, J = 9.1 720 + twenty-one No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 10.12 (s, 2H), 8.26 (d, 1H, J N4- (3-Chloro-4- = 4.7 Hz), 7.93 (s, 1H), 7.85 methoxyphenyl) -N2- [ l- (s, 1H), 7.78 (d, 1H, J = 2.6 722 (cyclohexylmethyl) indazole-Hz), 7.63 (d, lH, J = 8.8 Hz), + + 6-yl] -5-fluoro-2 , 4-7.58 (dd, 1H, J = 2.6 and 8.8 pyrimidmdiamine Hz), 7.19 (d, lH, J = 8.8 Hz), 7.11 (d, 1H, J = 8.8 Hz), 3.90 (d, 2H, J = 7.3 Hz), 3 * H NMR (DMSO-d6): d 10.05 (s, 1H), 9.91 (s, 1H), N2- [l- 8.29 (d, 1H, J = 4.1 HzO, (Cyclohexylmethyl) indazole 8.05 (d, 1H, J = 2.3 Hz), 7.92 723 -6-yl] -N4- (3,4- (s, 1H), 7.90 (s, 1H), 7.73 dichlorophenyl) -5-fluoro- (dd, 1H, J = 2.3 and 8.8 Hz), 8.8 Hz), 7.54 (d, 1H, J = 8.8 Hz), 7.21 (d, 1H, J = 8.8 Hz), 3.93 (d, 2H, XH NMR (DMSO-d6 ): d N2- [l-10.73 (s, 1H), 10.07 (s, 1H), (Cyclohexylmethyl) indazole 10.01 (s, 1H), 8.22 (d, 1H, J -6-yl) -N4- (2 , 2-dimethyl-3- = 4.7 Hz), 7.91 (s, 1H), 7.86 724 oxo-4H- (s, 1H), 7.60 (d, lH, J = 8.8 benz [l, 4] oxazin-6- il) -5- HzO, 7.26 (dd, 1H, J = 2.3 and fluoro-2.4- 8.5 Hz), 7.22-7.19 (app m, pir? nidindi amine 2H), 6.85 (d, lH, J = 8.5 Hz), 3.93 (d, 2H, J = 7.3 Hz), 1 XH NMR (DMSO-d6): d 10.24 (s, 2H), 8.29 (d, 1H , J N2- [l- = 4.7 Hz), 7.95 (s, 1H), 7.86 (Cyclohexylmethyl) indazole (s, 1H), 7.63 (d, 1H, J = 8.8 725 -6-yl) -5-fluoro- N4- (4- Hz), 7.49 (dd, 1H, J = 2.3 and fluoro-3-methoxyphenyl) - 8.8 Hz), 7.28-7.24 (m, 1H), 2,4-? Irin? Dmdiamine 7.19-7.12 ( m, 2H), 3.91 (d, 2H, J = 7.3 Hz), 3.55 (s, 3H), 1.75-1.73 (m, 1H), 1.54 (br! H NMR (DMSO-d6): d 10.40 (s, 1H), 10.26 (s, 1H), N4- (3-Chloro-4- 8.26 (d, 1H, J = 5.3 Hz), 7.91 methoxyphenyl) -N2- [l- (s, 1H), 7.81 (s, 1H), 7.75 (d, 26 (cyclobutylmethyl) indazole-1H, J = 2.6 Hz), 7.68 (d, lH, 5-yl] -5-fluoro-2,4-J = 9.1 Hz), 7.55 (dd, 1H, J = pyriridinediamine 2.6 and 2.6 and 8.8 Hz), 7.38 (d, 1H, J = 8.8 Hz), 7.09 (d, lH, J = 9.1 Hz), 4.39 No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Iono, 3pt? NMR (DMSO-d6): d 10.32 (s, 1H), 10.06 (s, 1H), N2- [1- 8.29 (d, 1H, J = 4.7 Hz), 8.00 (Cyclobutylmethyl) indazole- (s, 1H) , 7.93 (s, 1H), 7.84 (s, 727 5-yl] -N4- (3,4- 1H), 7.68 (d, 2H, J = 8.8 Hz), dichlorophenyl) -5-fluoro- 7.49 (d , 1H, J = 8.8 Hz), 7.41 2,4-pyrrmidindiamine (d, 1H, J = 8.8 Hz), 4.40 (d, 2H), 2.86-2.76 (m, 1H), 1.96-1.75 (m, 6H) . LCMS: * H NMR (DMSO-d6): d N2- [l- 10.79 (s, 1H), 10.40 (s, 1H), (Cyclobutylmethyl) indazole- 10.25 (s, 1H), 8.23 (d, 1H, J 5-yl] -N4- (2,2-dimethyl-3- = 4.9 Hz), 7.88 (s, 1H0, 7.86 728 oxo-4H- (s, 1H0, 7.64 (d, 1H, J = 8.8 + benz [ 1, 4] oxazin-6-yl) -5-Hz), 7.37 (d, lH, J = 9.1 Hz), fluoro-2,4- 7.21 (s, 1H), 7.18 (s, 1H), pyrimidiamine 6.86 (d, lH, J = 9.1 Hz), 4.37 (d, lH, J = 7.0 Hz), 2.83-2 * H NMR (DMSO-d6): d 10.48 (s, 1H), 10.36 (s, 1H), N2- [1- 8.29 (d, 1H, J = 5.3 Hz), 7.88 (Cyclobuylmethyl) indazole- (s, 1H), 7.86 (s, 1H0, 7.67 (d, 729 5-yl) -5-fluoro-N4 - (4- 1H, J = 8.0 Hz), 7.43 (dd, fluoro-3-methoxyphenyl) - 1H, J = 2.3 and 8.0 Hz), 7.35 2,4-pyrir dindiamine (dd, 1H, J = 1.8 and 8.8 Hz), 7.26-7.23 (m, 1H), 7.14 (dd, lH, J = 9.1 and ll.8 Hz), * H NMR (DMSO-d6): d 10.35 (s, 2H), 8.31 (d, 1H , J N4- (3-Chloro-4- = 4.7 Hz), 7.94 (s, 1H0, 7.86 methoxyphenyl) -N2- [l- (s, 1H), 7.78 (d, 1H, J = 2.3 730 (cyclobutylmethyl) indazole-Hz), 7.66 (d, lH, J = 8.8 Hz), 6-yl] -5-fluoro-2,4-7.57 (dd, 1H, J = 2.3 and 8.8 püimdindiamiua HzO, 7.16 (d, 1H, J = 8.8 Hz), 7.12 (d, 1H, J = 8.8 Hz), 4.09 (d, 2H, J = 7.3 Hz), 3 XH NMR (DMSO-d6 ): d 10.27 (s, 1H), 10.16 (s, 1H), N2- [l- 8.30 (d, 1H, J = 4.4 Hz), 7.99 (Cyclobutylmethyl) indazole- (d, 1H, J = 2.3 Hz) , 7.88 (s, 31 6-yl) -N 4 - (3,4- 1 H), 7.85 (s, 1 H), 7.67 (dd, + dichlorophenyl) -5-fluoro-1 H, J = 2.3 and 8.8 Hz), 7.60 2,4-pirjm? Idindiamine (d, 1H, J = 8.8 Hz), 7.51 (d, 1H, J = 8.8 Hz), 7.13 (d, 1H, J = 8.8 Hz), 4.07 (d, 2H, No Name of Compound Physical Data Triptase Tftasa Tftasa f_syk Com LD, LD, LD, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt * H NMR (DMSO-d6): d N2- [l-10.81 (s, 1H), 10.63 (s, 1H), (Cyclobutylmethyl) indazole-10.55 ( s, 1H), 8.33 (d, 1H, J6-ü) -N4- (2,2-dimethyl-3- = 5.3 Hz), 7.94 (s, 1H), 7.81 732 oxo-4H- (s, 1H ), 7.64 (d, 1H, J = 8.8 + benz [1,4] oxazin-6-yl) -5-Hz), 7.24-7.21 (m, 2H), 7.17 fluoro-2,4- (d, 1H) , J = 8.5 Hz), 6.86 (d, pyrimidinediamine 1H, J = 8.5 Hz), 4.12 (d, 2H, J = 7.0 Hz), 2.71-2.61 (m, lH NMR (DMSO-d6): d 10.67 (s) , 1H), 10.58 (s, 1H), N2- [l- 8.38 (d, 1H, J = 5.3 Hz), 7.96 (Cyclobuylmethyl) indazole- (s, 1H), 7.85 (s, 1H), 7.66 (d , 733 6-yl) -5-fluoro-N4- (4-1H, J = 8.5 Hz), 7.48 (dd, + fluoro-3-methoxyphenyl) - 1H, J = 2.3 and 8.5 Hz), 7.23-2, 4-? Nididiamine 7.11 (m, 3H), 4.07 (d, 2H, J = 7.0 Hz), 3.51 (s, 3H), 2.67- 2.57 (m, 6H). CLEM: ret. TI NMR (DMSO-d6): d 10.05 (s, 1H), 9.91 (s, 1H), N4- (3-Chloro-4- 8.31 (d, 1H, J = 5.2 Hz), 7.96 methoxyphenyl) -N2- [I- (s, 1 H), 7.87 (s, 1 H), 7.80 (s, 734 (cyclo? ro-methyl) indazole 1 H), 7.72 (d, I H, J = 8.8 Hz), -5-yl] -5- fluoro-2,4-7.60 (d, 1H, J = 8.8 Hz), 7.43 pyrir ^ indiamin (d, 1H, J = 9.1 Hz), 7.14 (d, 1H, J = 8.8 Hz), 4.31 (d, 2H , J = 7.0 Hz), 3.48 (s,! H NMR (DMSO-d6): d 10.39 (s, 1H), 10.14 (s, 1H), N2- [l- 8.31 (d, 1H, J = 4.7 Hz ), 8.05 (Cyclopropylmethyl) indazo (d, 1H, J = 2.3 Hz), 7.98 (s, 735 l-5-yl) -N4- (3,4- 1H), 7.89 (s, 1H), 7.73 (d , dichlorophemethyl) -5-fluoro-1H, J = 9.1 Hz), 7.54 (d, lH, 2,4-pyrimidinediamine J = 8.8 Hz), 7.45 (dd, 1H, J = 2.3 and 8.8 Hz), 4.32 (d , 2H, J = 7.0 Hz), 1.34-1.24 (m TÍ NMR (DMSO-d6): d N2- [l- 10.85 (s, 1H), 10.46 (s, 1H), (Cyclopro? Ilmethyl) indazo 10.29 ( s, 1 H), 8.23 (d, 1 H, J l-5-yl] -N 4 - (2,2-dimethyl- = 5.3 Hz), 7.95 (s, 1 H), 7.94 736 3-oxo-4 H- (s , 1H0, 7.71 (d, 1H, J = 9.1 + + benz [1,4] oxazin-6-yl) -5-Hz), 7.42 (dd, 1H, J = 2.3 and fl uoro-2.4- 9.1 Hz), 7.27 (d, 1H, J = 8.5 pyrimidine diamine Hz), 7.25 (s, 1H), 6.95 (d, 1H, J = 8.5 Hz), 4.32 (d, Compound Name Data Physical Triptase Triptase f syk LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 10.43 (s, 1H), 10.27 (s, 1H), N2- [l-8.31 (d, lH, J = 4.3 Hz), 7.95 (Cyclo? Ropilmethyl) indazo (s, 1H ), 7.94 (s, 1H), 7.71 (d, l-5-yl) -5-fluoro-N4- (4-1H, J = 9.1 Hz), 7.48 (dd, + fluoro-3-methoxyphenyl) - 1H , J = 2.3 and 8.8 Hz), 7.41 2,4-piri midindiamine (dd, 1H, J = 2.3 and 9.1 Hz), 7.31-7.29 (m, 1H), 7.30 (dd, lH, J = 8.8 and ll. l Hz), * H NMR (DMSO-d6): d 10.28 (s, 2H), 8.31 (d, 1H, J N4- (3-Chloro-4- = 4.3 Hz), 7.95 (s, 1H), 7.96 methoxyphenyl) -N2- [l- (s, 2H), 7.87 (s, 1H), 7.79 (d, (cyclopropylmethyl) indazole 1H, J = 2.6 Hz), 7.69 (d, lH, -6-yl) -5 -fluoro-2,4- J = 8.8 Hz), 7.58 (dd, 1H, J = pyrimidindiamine 2.6 and 9.1 Hz), 7.19 (dd, 1H, J = 1.8 and 8.8 Hz), 7.11 (d, 1H, J = 9.1 Hz), 4.32 T NMR (DMSO-d6): d 10.21 (s, 1H), 10.10 (s, 1H), N2- [l- 8.32 (d, 1H, J = 4.3 Hz), 8.04 (Cyclopropylmethyl) indazo (d, 1H, J = 2.6 Hz), 7.93 (s, l-6-yl] -N4- (3,4- 1H), 7.91 (s, 1H), 7.71 (dd, + dichlorophenyl) -5-fluoro - 1H, J = 2.6 and 8.8 Hz), 7.65 2.4-? Irir ^ indiamine (d, 1H, J = 8.8 Hz), 7 .54 (d, 1H, J = 8.8 Hz), 7.20 (d, lH, J = 8.8 Hz), 4.32 (d, 2H, * H NMR (DMSO-d6): d 10.82 (s, 1H), 10.22 ( s, 1H), N2- [1-10.16 (s, 1H), 8.31 (d, 1H, J (Cyclopro-ylmethyl) indazo = 4.7 Hz), 8.00 (d, 1H, J = 1-6-yl) - N4- (2,2-dimethyl- 0.8 Hz), 7.97 (s, 1H), 7.34 3-oxo-4H- + (d, 1H, J = 8.8 Hz), 7.35- + benz [1,4] oxazin- 6-yl) -5- 7.27 (m, 3H), 6.92 (d, 1H, J fluoro-2,4- = 8.5 Hz), 4.32 (d, 2H, J = pyrimidinediamine 7.0 Hz), 1.36 (s, 6H) ), 1.33-1.17 (m, * H NMR (DMSO-d6): d 10.23 (s, 2H), 8.31 (d, 1H, J N2- [l- = 4.9 Hz), 7.95 (s, 1H), 7.91 (Cyclopropylmethyl) indazo (s, 1H), 7.65 (d, 1H, J = 8.8 l-6-yl) -5-fluoro-N4- (4 Hz), 7.48 (dd, 1H, J = 2.3 and fluoro- 3-methoxyphenyl) - 8.8 Hz),, 7.29-7.24 (m, 1H), 2,4-pyrimidinediamine 7.20-7.13 (m, 3H), 4.09 (d, 2H, J = 6.7 Hz), 3.65 (s, 3H ), 1.33-1.17 (m, 1H), 0.55-0 or. Compound Name Physical Data Triptase Triptase Triptase f syk om LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt xHRMN (DMSO-d6): d 10.35 (s, 1H), 10.20 (s, 1H), N4- (3-Chloro-4- 8.24 (d, 1H, J = 5.3 Hz), 7.92 methoxyphenyl) -N2- (l- (s, 1H), 7.81 (s , 1 H), 7.74 (d, 742 cyclohexylindazol-5-yl) - 1 H, J = 2.6 Hz), 7.71 (d, 1 H, + 5-fluoro-2,4-J = 8.1 Hz), 7.55 (dd, 1 H , J = pyrimid diamine 2.6 and 8.8 Hz), 7.36 (dd, 1H, J = 1.8 and 8.8 Hz), 7.09 (d, 1H, J = 8.1Hz), 4.5 TÍRMNÍDMSO-dd ^ d 10.26 (s, 1H), 9.99 (s, 1H), N2- (l- 8.23 (d, 1H, J = 4.9 Hz), 7.96 Cyclohexylindazol-5-yl) - (s, 1H), 7.89 (s, 1H), 7.80 (s, 743) N 4 - (3,4-dichlorophenyl) -5- 1 H), 7.66 (d, 1 H, J = 8.1 Hz), + fluoro-2,4- 7.61 (app s, 1 H), 7.45 (d, 1 H, pyrimidinediamine J = 9.1Hz), 7.34 (d, lH, J = 9.1 Hz), 4.53-4.49 (m, 1H), 1.87-1.78 (m, 6H), 1.67 T RMNÍDMSO-do ^ d 10.80 (s, 1H), 10.36 (s, 1H), N2- (l- 10.15 (s, 1H), 8.21 (d, 1H, J Cyclohexylindazol-5-yl) - = 4.9 Hz), 7.89 (s, 1H), 7.86 N4- (2, 2-dimethyl-3-oxo-744 (s, 1H), 7.64 (d, lH, J = 9.4 + 4H-benz [1,4] oxazin-6 Hz), 7.36 (dd, lH, J = 2.3y il) -5-fluoro-2,4- 8.8 Hz), 7.18 (d, 1H, J = 2.3 pyrimidinediamine Hz), 6.86 (d, 1H, J = 9.4 Hz), 4.53-4.49 (, 1H), 1.89 TÍRMNtTJMSO-do ^ d 10.26 (s, 1H), 10.07 (s, 1H), N2- (l- 8.22 (d, lH, J = 5.0 Hz), 7.90 Cyclohexylindazol-5-yl) - (s, 1H), 7.89 (s, 1H), 7.67 (d, 745 5-fluoro-N4- (4-fluoro-3-1H, J = 8.8 Hz), 7.44 (dd, + methoxyphenyl) -2,4- 1 H, J = 8.5 Hz), 7.34 (dd, piriiiudindiarnin lH, J = 1.8y8.8Hz), 7.28- 7.24 (m, 1H), 7.15 (dd, 1H, J = 8.8 and 11.1 Hz), 4.53-4.4 TÍRMNODMSO-do ^ d 10.21 (s, 1H), 10.19 (s, 1H), N4- (3-Chloro-4- 8.28 (d, 1H, J = 4.9 Hz), 7.95 methoxyphenyl) -N2- (l- (s, 1H), 7.86 (d, lH, J = 2.6 746 cyclohexyldazol-6-yl) - Hz), 7.84 (s, 1H), 7.66 (d, 5-fluoro-2,4) - 1H, J = 8.5 Hz), 7.59 (dd, 1H, püimdindiarnin J = 2.6 and 9.1Hz), 7.21 (dd, lH, J = 1.8y8.5Hz), 7.06 (d, lH, J = 9.1Hz), 4.19 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d 10.05 (s, 1H ), 9.88 (s, 1H), N2- (1- 8.29 (d, 1H, J = 4.9 Hz), 8.11 Cyclob.exylindazol-6-yl) - (d, 1H, J = 2.6 Hz), 7.93 (s, 747 N4- (3,4-dichlorophenyl) -5- 1 H), 7.92 (s, 1H), 7.78 (dd, + fluoro-2,4- 1H, J = 2.6 and 8.8 Hz), 7.64 pyrimidiamine (d, 1H, J = 8.5 Hz), 7.51 (d, 1H, J = 8.8 Hz), 7.22 (dd, lH, J = 1.7 and 8.5 Hz), 4.19! H NMR (DMSO-d6): d 10.76 ( s, 1H), 10.25 (s, 1H), N2- (1-10.18 (s, 1H), 8.24 (d, 1H, J Cyclohexyldazole-6-yl) - = 4.9 Hz), 7.94 (s, 1H), 7.83 N4- (2,2-dimethyl-3-oxo- (s, 1H), 7.63 (d, 1H, J = 8.5 748 4H-benz [1,4] oxazin-6 Hz), 7.31-7.22 (m , 3H), 6.80 + ü) -5-fluoro-2,4- (d, 1H, J = 8.5 Hz), 4.23- pyrimidiamine 4.12 (m, 1H), 1.85-1.77 (m, 6H), 1.65 -1.62 (, 1H), 1.38 (s, T, NMR (DMSO-d6): d 10.02 (s, 1H), 9.95 (s, 1H), N2- (l- 8.26 (d, 1H, J = 4.3 Hz) , 7.93 Cyclohexyldazol-6-yl) - (s, 2H), 7.83 (s, 1H), 7.63 (d, 749 5-fluoro-N4- (4-fluoro-3-1H, J = 8.8 Hz), 7.55 ( dd, methoxyphenyl) -2,4- 1H, J = 2.6 and 8.8 HzO, 7.31- pyrimid diamine 7.28 (, 1H), 7.18 (d, 1H, J = 8.8 Hz), 7.12 (dd, 1H, J = 8.8 and 11.4 Hz), 4.11-4.00 XH NMR (DMSO-d6): d 12.23 (s, 1H), 9.53 ( s, 1H), 9.36 (s, 1H), 8.14 (d, 1H, J = N4- (3,4-Dichlorophenyl) -5- 3.5 Hz), 8.10 (d, 1H, J = 2.7 fluoro-N2- ( 3-750 Hz), 7.88 (s, 1H), 7.86 (dd, methylindazol-6-yl) -2,4- + 1H, J = 2.7 and 8.8 Hz), 7.47 pñ ± rnidindiamine (d, 2H, J = 8.8 Hz), 7.16 (dd, 1H, J = 1.8 and 8.8 Hz), 2.36 (s, 3H). LCMS: ret. time X H NMR (DMSO-d 6): d 10.62 (s, 1 H), 9.63 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo- 9.44 (s, 1 H), 8.13 (d, 1 H, J = 4 H -benz [1,4] oxazin-6- 41. Hz), 7.84 (s, 1 H), 7.50 751 il) -5-fluoro-N 2 - (3- (d, 1 H, J = 8.8 Hz) , 7.36 (dd, + + methylindazole-6 ~ il) -2,4- 1H, J = 2.3 and 8.5 Hz), 7.31 pyridoidimethylamine (d, 1H, J = 2.3 Hz), 7.24 (dd, 1H, J = 1.8 and 8.8 Hz), 6.89 (d, 1H, J = 8.5 Hz), 2.41 No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, ID, ID, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Iono, 3pt? NMR (DMSO-d6): d 10.49 (s, 1H), 10.43 (s, 1H), N4- (3-Chloro-4-3.33 (d, 1H, J = 5.3 Hz), 7.77 methoxyphenyl) -N2- ( l, 3- (d, 1H, J = 2.6 Hz), 7.67 (d, 752 dimethylindazol-6-yl) -5- 1H, J = 1.2 Hz), 7.62 (d, lH, + + fluoro-2,4- J = 8.8 Hz), 7.55 (dd, 1H, J = pyrimidinediamine 2.6 and 8.8 Hz), 7.10 (d, 1H, J = 8.8 Hz), 7.09 ( d, 1H, J = 8.8 Hz), 3.83 (s, 3H), XH NMR (DMSO-d6): d 9.65 (s, 1H), 9.50 (s, 1H), 8.22 (d, 1H, J = 3.5 H ), 8.12 (d, lH, J N4- (3,4-Dichlorophenyl) - = 2.3 Hz), 7.91 (d, 1H, J = N2- (1, 3-dimethylindazole-753 1.8 Hz), 7.79 (dd, 1H, J = 2.3 6-ü) -5-fluoro-2,4- + + and 8.8 Hz), 7.52 (dd, 2H, J = pyrimid diamine 2.3 and 8.8Hz), 7.18 (dd, 1H, J = 1.8 and 8.8 Hz), 3.69 (s, 3H), 2.39 (s, 3H) XH NMR (DMSO-d6): d 10.72 (s, 1H), 10.25 (s, 2H), N2- (1, 3-Dimetiindazole- 8.26 (d, 1H, J = 4.9 Hz), 7.72 6-yl) -N4- (2,2-dimethyl-3- (s, 1H), 7.57 (d, 1H, J = 8.5 oxo-4H- 754 Hz ), 7.25 (dd, 1H, J = 2.3 and + benz [1,4] oxazin-6-yl) -5- + + 8.5 Hz), 7.22 (app s, 1H), fluoro-2,4- 7.14 ( dd, 1H, J = 2.3 and 8.5 pirunidindiamine Hz), 6.87 (d, lH, J = 8.5 Hz), 3.37 (s, 3H), 2.40 (s, 3H lH NMR (DMSO-d6): d 10.14 (s, 2H), 8.28 (d, 1H, J = 3.7 Hz), 7.79 (d, 1H, J = N2- (l, 3-Dimethyl) ndazol- 1.8 Hz), 7.57 (d, 1H, J = 8.5 6-yl) -5-fluoro-N4- (4-755 Hz), 7.48 (dd, 1H, J = 2.3 and fluoro-3-methoxyphenyl) - + 8.5 Hz), 7.31-7.26 (m, 1H), 2,4-? Irirnidindiamiaa 7.17 (dd, 1H, J = 8.8 and 11.4 Hz), 7.10 (dd, 1H, J = 1.8 and 8.8 Hz), 3.66 ( s, 3H), 3.6 X H NMR (DMSO-d 6): d 10.44 (s, 1H), 9.89 (s, 1H), 8.21 (d, 1H, J = 5.6 Hz), 7.97 N4- (3-Chloro-4) - (s, 1H), 7.70 (s, 1H), 7.62 (s, methoxyphenyl) -N2- (1, 6- 1H), 7.58 (s, 1H), 7.46 (d, 56 dimethylindazol-5-yl) - 5 - 1 H, J = 8.5 Hz), 6.91 (d, 1 H, fluoro-2,4-J = 8.5 Hz), 4.00 (s, 3 H), pmmidindiamine 3.75 (s, 3 H), 2.32 (s, 3 H). CLEM: ret time: 9.25 min.; No. Name of Compound Physical Data Tftase Triptase Triptase f syk Com LD, ID, ID, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt? NMR (DMSO-d6): d 10.34 (s, 1H), 9.70 (s, 1H), 8.24 (d, 1H, J = 4.7 Hz), 7.97 N4- (3,4-Dichlorophenyl) - (s, 1H) 7.87 (s, 1H), 7.68 (s, N2- (1, 6-dimethylindazole-1H), 7.58 (s, 1H), 7.55 (d, 757, 5-yl) -5-fluoro-2,4-1H , J = 8.5 Hz), 7.37 (d, 1H, pyrimidinediamine J = 8.5 Hz), 4.01 (s, 3H), 2.32 (s, 3H). CLEM: time ret. 11.58 min .; purity: 91%; T NMR (DMSO-d6): d 10.70 (s, VB), 10.51 (s, 1H), N2- (1, 6-dimethylindazole-8.16 (d, 1H, J = 4.9 Hz), 7.95 5-yl) - N4- (2,2-dimethyl-3- (s, 1H), 7.74 (s, 1H), 7.55 (s, oxo-4H-758 1H), 7.17 (d, 1H, J = 8.5 Hz), + benz [1, 4] oxazin-6-yl) -5- 6.69 (d, 1H, J = 8.5 Hz), 4.00 fluoro- 2,4- (s, 3H), 2.34 (s, 3H), 1.31 (s, pyrimidindiamine 6H). CLEM: time ret. 8.24 min .; purity: 96%; T NMR (DMSO-d6): d 10.42 (s, 1H), 9.84 (s, 1H), 8.18 (d, 1H, J = 3.9 Hz), 7.96 N2- (1, 6-dimethylindazole- (s, 1H) , 7.74 (s, 1H), 7.57 (s, 5-yl) -5-fluoro-N4- (4-1H), 7.45 (d, lH, J = 8.5 Hz), 759 + fluoro-3-methoxyphenyl) - 7.20 (m, 1H), 6.97 (m, 1H), 2,4-pminidindiamine 4.02 (s, 3H), 3.55 (s, 3H), 2.33 (s, 3H). CLEM: time ret. 9.33 min; purity: 96%; X H NMR (DMSO-d 6): d 10.25 (s, 1 H), 10.06 (s, 1 H), 8.36 (d, 1 H, J = 1.8 Hz), 8.30 N 4 - (3,4-Dichlorophenyl) - (d, 1 H , J = 4.4 Hz), 8.03 (d, N2- (2-ethylindazol-6-yl) -760 1H, J = 2.3 Hz), 7.86 (s, lH), + 5-fluoro-2,4- 7.82 ( dd, 1H, J = 2.6 and 8.8 pyrimidinediamine Hz), 7.66 (d, lH, J = 8.8 Hz), 7.53 (d, 1H, J = 8.8 Hz), 7.14 (dd, lH, J = 1.8 and? NMR ( DMSO-d6): d 10.57 (s, 1H), 9.51 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.30 (s, 1H), 8.21 (s, 1H), 4H-benz [1,4] oxazin-6- 8.12 (d, lH, J = 4.1 Hz), 8.07 761 il) -N2- (2-ethylindazole-6- (s, 1H), 7.51 (d, 1H, J = 9.1 + + il) -5-fluoro-2,4-Hz), 7.40 (d, lH, J = 2.3 Hz), pñjmñdindiamine 7.27 (dd, 1H, J = 2.3 and 8.8 Hz), 7.11 (dd, 1H, J = 1.8 and 9.1 Hz), 6.89 (d, lH, J = No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com ID, LD, ID, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt l H NMR (DMSO-d 6): d 10.14 (s, 1 H), 9.82 (s, 1 H), 8.25 (d, 1 H, J = 4.4 N 4 - (3,4-Dichlorophenyl) -5 Hz), 8.22 (s) , 1H), 8.06 (d, fluoro-N2- (2-t j- 1H, J = 2.3 Hz), 7.83 (s, 762 + + 763 + 764 + 765 + No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, ID, ID, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.69 (s, 1H) , 10.09 (s, 1H), 9.88 (s, 1H), 8.21 (d, 1H, J = 4.7 Hz), 7.91 (d, 1H, J = 0.8 Hz), 7.83 (s, 1H), 7.61 (d, 1H, J = 8.5 Hz), 7.29 (dd, DL-1H acid salt, J = 2.3 and 8.5 Hz), 7.17 camphor-1-sulphonic of (dd, 1H, J = 2.3 and 8.5 Hz), N4- ( 2,2-Dimethyl-3-oxo- 7.13 (d, 1H, J = 2.3 Hz), 6.85 766 4H-benz [1,4] oxazin-6- (d, 1H, J = 8.5 Hz), 3.80 (s) , + ü) -5-fluoro-N2- (l- 3H), 2.87 (d, 1H, AB qt, J = methylindazol-6-yl) -2.4- 14.6 Hz), 2.26-2.18 (m, 1H ), pyridinediamine 1.92 (br t, 1H, J = 4.7 Hz), 1.88-1.83 (m, 2H), 1.38 (s, 6H), 1.32-1.21 (, 2H), 1.03 (s, 3H), 0.73 (s, 3H). CLEM: time ret. 9.53 ruin; purity: 94%; MS (m / e): 434 (MH +) X H NMR (DMSO-d 6): d Acid salt 10.70 (s, 1 H), 10.22 (s, 1 H), ethanesulfonic acid of N 4 - 10.00 (s, 1 H), 8.24 ( d, 1H, J (2,2-Dimethyl-3-oxo-4H- = 4.9 Hz), 7.92 (d, 1H, J = 767 benzfl, 4] oxazin-6-yl) -5- 0.8 Hz), 7.80 (s, 1H), 7.63 fluoro-N2- (l- (d, 1H, J = 8.8 Hz), 7.28 (dd, methylindazol-6-yl) -2.4- 1H, J = 2.3 and 8.8 Hz), 7.16 pyrimidmdiamine (d, 1H, J = 1.8 and 8.5 Hz), 7.11 (d, lH, J = 2.3 Hz), 6.8 XH NMR (DMSO-d6): d P-10.69 acid salt (s, 1H), 10.17 (s, 1H), hydroxybenzenesulfonic 9.92 (s, 1H), 8.21 (d, 1H, J = of N4- (2,2-Dimethyl-3- 4.7 Hz), 7.92 (d, 1H, J = 0.8 oxo-4H - 768 Hz), 7.81 (s, 1H), 7.62 (d, benz [1,4] oxazin-6-yl) -5- 1 H, J = 8.5 Hz), 7.38 (td, 2H, fluoro-N2- ( l- J = 2.6 and 8.8 Hz), J = 7.28 methylindazol-6-yl) -2,4- (dd, 1H, J = 2.3 and 8.5 Hz), pyrirnidinediamine 7.16 (d, lH, J = 1.8 and 8) NMR (DMSO-d6): d 10.70 (s, 1H), 10.28 (s, 1H), acid salt 10.00 (s, 1H), 8.22 (d, 1H, benzenesulfonic J of N4- = 4.9 Hz), 7.94 ( d, 1H, J = (2.2 -Dimethyl-3-oxo-4H- 0.8 Hz), 7.78 (s, 1H), 7.64 69 benz [l, 4] oxazin-6-yl) -5- (d, 1H, J = 8.8 Hz), 7.60- fluoro-N2- (l- 7.56 (m, 2H), 7.33-7.26 (, methuindazol-6-yl) -2.4- 4H), 7.15 (d, 1H, J = 1.8 and pyrimidiadiaxin 8.5 Hz), 7.10 ( d, 1H, J = 2.3 Hz), No. Name of Compound Physical Data Triptase Triptase Triptase f_syk Com LD, LD, ID, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt! H NMR (DMSO-d6): d 10.74 (s, 1H), 10.21 (s, 2H), N4- ( 2,2-Dimethyl-3-oxo- 8.26 (d, 1H, J = 4.9 Hz), 7.92 4H-benz [1,4] oxazin-6- (d, 1H, J = 0.8 Hz), 7.82 (s, il) -5-fluoro-N2- (l- 770 1H), 7.62 (d, lH, J = 8.8 Hz), methylindazol-6-yl) -2.4-7.27 (dd, 1H, J = 2.3 and 8.5 pyrirm ^ diamine Hz), 7.21 (d, lH, J = 2.3 Hz), Hydrochloric Acid Salt 7.18 (dd, 1H, J = 1.8 and 8.5 Hz), 6.86 (d, 1H, J = Tí NMR (DMSO-d6) : d 10.18 (s, 1H), 9.91 (s, 1H), 8.21 (d, 1H, J = 4.7 Hz), 7.98 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.3 Hz ), 7.90 (s, fluoro-N2- [1- (2-771 1H), 7.81 (s, 1H), 7.66 (app methoxyethyl) indazol-5-yl] - + d, 1H, J = 8.8 Hz), 7.60 (d, 2,4-pyridibindiamine 1H, J = 9.1 Hz), 7.46 (d, lH, J = 9.1 Hz), 7.37 (dd, 1H, J = 2.3 and 8.8 Hz), 4.48 (t, X H NMR (DMSO-d 6): d 10.45 (s, 1 H), 10.33 (s, 1 H), N 4 - (3-Chloro-4- 8.27 (d, 1 H, J = 4.9 Hz), 7.93 methoxyphenyl) -5- fluoro- (s, 1H), 7.81 (d, 1H, J = 1.5 772 N2- [l- (2- Hz), 7.74 (d, 1H, J = 2.3 Hz), + + methoxyethyl) indazol-5-yl] - 7.65 (d, 1H, J = 8.8 Hz), 7.54 2,4-pyrimidinediamine (dd, 1H, J = 2.3 and 9.1 Hz), 7.37 (dd, 1H, J = 2.6 and 9.1 Hz), 7.10 (d, 1H, J = lH NMR (DMSO-d6): d 10.78 (s, 1H), 10.35 (s, 1H), N4- (2,2-Dimethyl-3-oxo-10.19 (s, 1H), 8.21 (d, 1H, J 4H-benz [1,4] oxazin-6- = 4.9 Hz), 7.90 (s, 1H), 7.87 773 il) -5-fluoro-N2- [l- (2- (s, 1H), 7.60 (d, 1H, J = 8.8 + + methoxyethyl) indazol-5-yl] - Hz), 7.36 (dd, 1H , J = 1.8 and 2,4-pyrimidinediamine 8.8 Hz), 7.21 (dd, 1H, J = 1.8 and 8.5 Hz), 7.17 (s, 1H), 6.87 (d, lH, J = 8.5 Hz), * H NMR (DMSO-d6): d 10.19 (s, 1H), 9.93 (s, 1H), 8.20 (d, 1H, J = 4.7 Hz), 7.90 5-Fluoro-N4- (4-fluoro- (s, 2H) 7.61 (d, 1H, J = 8.8 3-methoxyphenyl) -N2- [l- (2-74 Hz), 7.44 (dd, 1H, J = 2.6 and methoxyethyl) indazol-5-yl] - 8.8 Hz), 7.37 (dd, 1H, J = 2.0 2,4-pyrradi-diamine and 8.8 Hz), 7.29-7.26 (m, 1H), 7.13 (dd, 1H, J = 8.8 and 11.1 Hz), 4.53 (t, 2H, J No Compound Name Physical Data Triptase Triptase Triptase f_syk Co m LD, LD, ID, llpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt lH NMR (DMSO-d6): d 10.08 (s, 1H), 9.96 (s, 1H), 8.26 (d, 1H, J = 4.4 Hz), 8.03 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.3 Hz), 7.91 (d, fluoro-N2- [l- (2-775 1H, J = 0.8 Hz), 7.82 (s, lH), + + methoxyethyl) indazol-6-yl] - 7.70 (dd, 1H, J = 2.3 yy 8.8 2,4-? Irirm ^ indiamina Hz), 7.60 (d, lH , J = 8.8 Hz), 7.49 (d, 1H, J = 8.8 Hz), 7.19 (dd, lH, J = 1.8a T NMR (DMSO-d6): d 10.02 (brs, 2H), 8.24 (d, lH , N4- (3-Chloro-4- J = 4.7 Hz), 7.95 (d, 1H, J = methoxyphenyl) -5-fluoro- 0.8 Hz), 7.83 (s, 1H), 7.79 776 N2- [l- ( 2- (d, 1H, J = 2.6 Hz), 7.63 (d, methoxyethyl) indazol-6-yl] - 1 H, J = 8.8 Hz), 6.59 (dd, 2,4-? Irimidindiamine 1H, J = 2.6 and 9.1 Hz), 7.21 (dd, 1H, J = 1.8 and 8.8 Hz), 7.09 (d, lH, J = 9.1Hz), 4.2 XH NMR (DMSO-d6): d 10.71 (s, 1H), 10.18 (br s, N4- (2,2-Dimethyl-3-oxo-2H), 8.20 (d, lH, J = 4.9 Hz), 4H-benz [1,4] oxazin-6- 7.91 (d, 1H, J = 0.8 Hz), 7.75 777 ü) -5-fluoro-N2- [l- (2- (s, 1H), 7.57 (d, 1H, J = 8.5 + methoxyethyl) ind azol-6-yl] - Hz), 7.23-7.15 (m, 3H), 6.81 2,4-? irin? idindiamine (d, 1H, J = 8.8 Hz), 4.24 (t, 2H, J = 5.3 Hz) , 3.61 (t, 3H, J = 5.3 Hz), 3.06 (s, 3H), JH NMR (DMSO-d6): d 9.92 (brs, 2H), 8.23 (d, lH, J = 4.4 Hz), 7.94 ( d, 1H, J = 5-Fluoro-N 4 - (4-fluoro-0.8 Hz), 7.91 (s, 1H), 7.59 3-methoxyphenyl) - N 2 - [1-788 (d, 1H, J = 8.5 Hz) , 7.48 (dd, + (2-methoxyethyl) indazole-6- 1H, J = 2.6 and 8.8 Hz), 7.34- ü] -2,4-pyrimidmidomine 7.30 (m, 1H), 7.21 (dd, 1H, J = 1.8 and 8.8 Hz), 7.15 (dd, lH, J = 8.8yll! Hz), T NMR (DMSO-d6): d 10.39 (s, 1H), 10.27 (s, 1H), N4- (3-Chloro- 4- 8.26 (d, 1H, J = 4.9 Hz), 7.93 methoxyphenyl) -5-fluoro- (s, 1H), 7.81 (d, 1H, J = 1.4 779 N2- [l- (l-Hz), 7.74 (d, lH, J = 2.3 Hz), + methylethyl) indazol-5-yl] - 6.67 (d, H, J = 9.1 Hz), 7.54 2,4-pyriridinediamine (dd, 1H, J = 2.3 and 9.1 Hz ), 7.37 (dd, 1H, J = 1.8 and 8.8 Hz), 7.09 (d, 1H, J = No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, ID, LD, Lpt CHMC, CHMC, CHMC, IgE, 3pt IgE, 8pt Iono, 3? T Tí NMR (DMSO-d6): d 10.20 (s), 1H), 9.91 (s, 1H), 8.26 (d, 1H, J = 4.7 Hz), 8.02 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.3 Hz), 7.94 (s , fluoro-N2- [l- (l- 780 1H), 7.86 (s, 1H), 7.68 (d, methylethyl) indazol-5-yl] - 1H, J = 8.8 Hz), 7.66 (d, lH, 2 , 4-piirinidindiamine J = 9.1Hz), 7.50 (d, 1H, J = 8.8 Hz), 7.41 (dd, 1H, J = 1.8 and9.1Hz), 4.95 (q, 1H, T, NMR (DMSO-d6): d 10.76 (s, 1H), 10.32 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 10.11 (s, 1H), 8.19 (d, 1H, J 4H-benz [l, 4] oxazin-6- = 5.3 Hz), 7.90 (s, 1H), 7.89 781 il) -5-fluoro-N2- [l- (l- (s, 1H), 7.62 (d, 1H, J = 8.8 + methylethyl ) indazol-5-yl] - Hz), 7.36 (dd, 1H, J = 1.8 and 2,4-pi? rirmdindiamine 8.8 Hz), 7.19 (d, 2H, J = 8.9 Hz), 6.87 (d, lH, J = 8.8 Hz), 4.91 (q, 1H, J = 6.4H XH NMR (DMSO-d6): d 10.35 (s, 1H), 10.21 (s, 1H), 8.25 (d, 1H, J = 4.9 Hz) , 7.90 5-Fluoro-N4- (4-fluoro- (s, 1H), 7.88 (s, 1H), 7.65 (d, 3-methoxyphenyl) - N2- [l- 782 1H, J = 8.1 Hz), 7.43 (dd, (l-methylethyl) indazole-5- + 1H, j = 2.3 and 8.8 Hz), 7.35 il] -2,4-pyrimidinediamine (dd, 1H, J = 1.8 and 8.8 Hz), 7 .26-7.22 (m, 1H), 7.14 (dd, lH, J = 8.8yll.lHz), XH NMR (DMSO-d6): d 10.10 (s, 2H), 8.25 (d, 1H, J N4- ( 3-Chloro-4- = 4.7 Hz), 7.93 (s, 1H), 7.86 methoxyphenyl) -5-fluoro- (s, 1H), 7.78 (d, 1H, J = 2.3 783 N2- [l- (l- Hz), 7.64 (d, lH, J = 8.8 Hz), methyethyl) indazol-6-yl] - 7.56 (dd, 1H, J = 2.3 and 8.8 2,4-pyrimidinediamine Hz), 7.18 (d, lH, J = 8.8Hz), 7.10 (d, 1H, J = 8.9 Hz), 4.45 (q, lH, J = 6.4Hz), T NMR (DMSO-d6): d 10.06 (s, 1H), 9.93 (s, 1H ), 8.30 (d, 1H, J = 4.3 Hz), 8.06 N4- (3, 4-Dichlorophenyl) -5- (d, 1H, J = 2.3 Hz), 7.93 (s, fluoro-N2- [l- ( l- 84 2H), 7.76 (dd, 1H, J = 2.3 and methylethyl) indazol-6-yl] - 8.8 Hz), 7.64 (d, 1H, J = 8.8 2,4-pyrimidinediamine Hz), 7.54 (d, lH, J = 8.8 Hz), 7.21 (dd, 1H, J = 1.8 and 8.8 Hz), 4.55 (q, 1H, J = 6 No. Compound Name Physical Data Tftasa Tftasa Triptase f syk Com ID, ID, ID, CHIT lpt, CHMC, CHMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d 10.76 (s, 1H), 10.14 (s, 2H), N4- (2 , 2-Dimethyl-3-oxo-8.24 (d, 1H, J = 4.9 Hz), 7.93 4H-benz [1,4] oxazin-6- (s, 1H), 7.88 (s, 1H), 7.61 (d , 785 il) -5-fluoro-N2- [l- (l-1H, J = 8.8 Hz), 7.27-7.16 methylethyl) indazol-6-yl] - (m, 3H), 6.88 (d, lH, J = 8.8 2,4-pyrimidindiamine Hz), 4.50 (q, 1H, J = 6.4 Hz), 1.37 (d, 6H, J = 6.4 Hz), 1.35 (s, 6H). CLEM: t. ret. X H NMR (DMSO-d 6): d 10.77 (s, 1 H), 10.14 (s, 1 H), (S) -N 4 - [2-Methyl-3-oxo-9.93 (s, 1 H, 8.22 (d, 1 H, J = 2 H, 4 H -benz [1,4] oxazin- 4.7 hz), 7.93 (s, 1 H), 7.92 (s, 786 6-yl] -5-fluoro-N 2 - [l- (1 H), 7.60 (d, lH, J = 8.5 Hz), + metiletü) indazol-6-yl] - 7.27 (dd, 1H, J = 2.3 and 8.5 2,4-pyripidinediamine HzO, 7.21-7.16 (m, 2H), 6.90 (d, 1H, J = 8.5 Hz), 4.65 (qt, lH, J = 6.7 Hz), 4.4 1 H NMR (DMSO-d6): d 10.17 (s, 1H), 9.90 (s, 1H), N2- [ 1- (3- 8.21 (d, 1H, J = 4.7 Hz), 7.97 Acetyloxypropyl) indazole- (d, 1H, J = 2.3 Hz), 7.90 (dd, 787 5-yl) -N4- (3, 4-1H, J = 2.3 and 8.8 Hz), 7.59 + + dichlorophenyl) -5-fluoro- (d, 1H, J = 8.8 Hz), 7.47 (d, 2,4-? Irinidinediamine 1H, J = 8.8 Hz) , 7.38 (dd, 1H, J = 2.0 and 8.8 Hz), 4.41 (d, 2H, J = 6.7 Hz), 3.88 1H NMR (DMSO-d6): d 10.32 (s, 1H), 10.19 (s, 1H) , N2- [l- (3-3.24 (d, 1H, J = 5.3 Hz), 7.93 Acetyloxypropyl) indazole- (s, 1H), 7.85 (s, 1H), 7.74 (d, 788 5-yl) -N4 - (3-chloro-4-1H, J = 2.3 Hz), 7.63 (d, 1H, methoxyphenyl) -5-fluoro-J-8.8 Hz), 7.54 (dd, 1H , J = 2,4-pyrimidmdiamine 2.3 and 9.1 Hz), 7.40 (dd, 1H, J = 2.3 and 8.8 Hz), 7.09 (d, 1H, J = 9.1 Hz), 4. 1H NMR (DMSO-d6): d 10.31 (s, 1H), 10.15 (s, 1H), N2- [l- (3- 8.24 (d, 1H, J = 4.7 Hz), 7.91 Acetyloxypropyl) indazole- (s, 2H), 7.61 (d, 1H, J = 8.8 789 5-yl] -5-fluoro-N4- (4 Hz), 7.44 (dd, 1H, J = 2.3 and + fluoro-3-methoxyphenyl) - 8.8 Hz), 7.38 (dd, 1H , J = 1.8 2,4-pyrimid diamine and 9.1 Hz), 7.27-7.25 (m, 1H), 7.15 (dd, 1H, J = 8.8 and 11.1 Hz), 4.45 (t, 2H, J No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com ID, LD, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 9.96 (s, 1H), 9.83 (s, 1H), N2- [1- (3-3.27 (d, 1H, J = 4.1Hz), 8.09 Acetyloxy? il) indazole- (d, 1H, J = 2.3 Hz), 7.94 (s, 790 6-yl) -N4- (3.4-1H), 7.92 (s, 1H), 7.75 (dd, + + dichlorophenyl) -5-fluoro- 1H, J = 2.3 and 8.8 Hz), 7.63 2,4-pyrin-dindiamine (d, 1H) , J = 8.8 Hz), 7.53 (d, 1H, J = 8.8 Hz), 7.23 (dd, lH, J = 1.8and8.8Hz), 4.20 1H NMR (DMSO-d6): d 10.68 (s, 1H), 9.84 (s, 1H), N4- (2,2-Dimethyl-3-oxo-9.74 (s, 1H), 8.18 (d, 1H, J = 4H-benz [1,4] oxazin-6- 4.4 Hz) , 7.90 (s, 1H), 7.56 (s, 791 il) -5-fluoro-N2- [l- (3-1H), 7.58 (d, 1H, J = 8.8 Hz), + + hydroxy? Ropil) indazole -6- 7.32-7.24 (m, 3H), 6.85 (d, ü] -2,4-pir ^ dindiamine 1H, J = 8.8 Hz), 4.20 (t, 2H, J = 6.7 Hz), 3.29 (t, 2H, J = 6.4 Hz), 1.87 (app q, 2H 1H NMR (DMSO-d6): d 10.42 (s, 1H), 10.30 (s, 1H), N4- (3-Chloro-4- 8.26 (d, 1H, J = 5.2 Hz), 7.93 methoxyphenyl) -5-fluoro- (s, 1H), 7.82 (d, 1H, J = 1.8 792 N2- [l- (3 Hz), 7.74 (d, 1H, J = 2.3 Hz) , + + + methoxypropyl) indazol-5- 7.60 (d, lH, J = 9.1Hz), 7.53 ü] -2,4-pi? imidindiamine (dd, 1H, J = 2.3 and 9.1 Hz), 7.38 (dd, 1H, J = 1.8 and 9.1 Hz), 7.09 (d, 1H, J = 9 1H NMR (DMSO-d6): d 10.36 (s, 1H), 10.13 (s, 1H), 8.30 (d, lH, J = 5.0 Hz), 8.01 N4- (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.3 Hz), 7.95 (s, fluoro-N2- [l- (3-793 1H), 7.86 (s, 1H), 7.68 (dd, + + methoxypropyl) indazole-5-1H, J = 2.3 and 8.8 Hz), 7.61 ü] -2,4-pyrimidinediamine (d, 1H, J = 9.1Hz), 7.51 (d, 1H , J = 8.8 Hz), 7.41 (dd, lH, J = 1.8y9.1Hz), 4.4 1H NMR (DMSO-d6): d 10.77 (s, 1H), 10.42 (s, 1H), N4- (2, 2-Dimethyl-3-oxo- 10.27 (s, 1H), 8.23 (d, 1H, J 4H-benz [1,4] oxazin-6- = 4.3 Hz), 7.90 (s, 1H), 7.88, 94 il) -5-fluoro-N2- [l- (3- (s, 1H), 7.56 (d, 1H, J = 8.8 + + methoxy? Ropil) indazole-5 Hz), 7.37 (dd, 1H, J = 1.8 and il] -2,4-? irimidindiamine 8.8 Hz), 7.21 (appd, 2H, J = 9.1 Hz), 6.87 (d, 1H, J = 9.1 Hz), 4.39 (t, 2H, J = 6.

No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion3pt 1 H NMR (DMSO-d 6): d 10.73 (s, 1H), 10.32 (s, 1H), (S) -5-Fluoro-N2- [1- (3-10.15 (s, 1H), 8.17 ( d, 1H, J methoxypropyl) indazole-5- = 4.9 Hz), 7.85 (s, 1H), 7.83 il] -N4- (2-methyl-3-oxo- 795 (s, 1H), 7.51 (d, 1H , J = 8.8 + 2H, 4H-benz [1,4] oxazin- + Hz), 7.33 (dd, 1H, J = 2.1 and 6-il) -2.4- 9.1 Hz), 7.16 (dd, 2H, J = 2.3 pyridine diamine and 9.1 Hz), 6.84 (d, 1H, J = 8.8 Hz), 4.60 (qt, 1H, 1H NMR (DMSO-d6): d 10.16 (s, 2H), 8.27 (d, 1H, J N4- (3-Chloro-4- = 4.7 Hz), 7.95 (d, 1H, J = methoxyphenyl) -5-fluoro- 0.8 Hz), 7.80 (s, 1H), 7.78 796 N2- [l- (3- (d, 1H, J = 8.8 Hz), 7.65 (d, + methoxypropyl) indazole-6- 1H, J = 2.3 and 9.1 Hz), 7.58 ü] -2,4-pyri-dindiamine (dd, 1H, J = 2.3 and 9.1 Hz), 7.20 (dd, 1H, J = 1.8 an 8.8 Hz), 7.09 (d, lH, J = 9.1 Hz), 1 H NMR (DMSO-d6): d 10.13 (s, 1H), 10.02 ( s, 1H), N4- (3,4-Dichlorophenyl) -5- 8.31 (d, lH, J = 4.1 Hz), 8.06 (d, 1H, J = 2.3 Hz), 7.95 (s, fluoro-N2- [ l- (3-797 1H), 7.87 (s, 1H), 7.74 (dd, methoxypropyl) indazol-6- 1H, J = 2.3 and 8.8 Hz), 7. 65 ü] -2,4-pyrimidiamine (d, 1H, J = 8.5 Hz), 7.54 (d, 1H, J = 8.8 Hz), 7.22 (d, lH, J = 8.5 Hz), 4.17 (t, 2H, 1 H NMR (DMSO-d 6): d 10.73 (s, 1 H), 9.92 (s, 2 H), N 4 - (2,2-Dimethyl-3-oxo-8.21 (d, 1 H, J = 4.7 Hz), 7.92 4 H -benz [1,4] oxazin-6- (s, 1H), 7.89 (s, 1H), 7.58 (d, 798 il) -5-fluoro-N2- [l- (3-1H, J = 8.8 Hz ), 7.29-7.24 + + methoxypropyl) indazol-6- (m, 3H), 6.85 (d, 1H, J = 8.5 il] -2,4-pirm? Idindiamine Hz), 4.17 (t, 2H, J = 6.7 Hz), 3.14 (app qt, 2H, J = 6.4 Hz), 3.13 (s, 3H), 1.92 (app 1H NMR (DMSO-d6): d 10.76 (s, 1H), 10.11 (s, 2H), ( S) -5-Fluoro-N2- [l- (3- 8.23 (d, 1H, J = 4.7 hz), 7.94 methoxypropyl) indazole-6- (s, 1H), 7.86 (s, 1H), 7.62 (d , il] -N4- (2-methyl-3-oxo- 799 1H, J = 8.5 Hz), 7.28-7.19 2H, 4H-benz [1,4] oxazin- + + (m, 3H), 6.88 (d , 1H, J = 8.5 6-il) -2.4-Hz), 4.64 (qt, 1H, J = 6.7 pmmidindiamine Hz), 4.17 (t, 2H, J = 6.7 Hz), 3.16 (app qt, 2H, J = 6.7 Hz No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, ID, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.17 (s, 1H), 8.20 (d, 1H, J N4- (3-Chloro-4- = 4.9 Hz), 7.85 (s, 1H), 7.69 methoxyphenyl) -5-fluoro- (d, 1H, J = 2.3 Hz), 7.61 (d, 800 N2- (2-trifluoromethyl-1H-1H, J = 8.8 Hz), 7.59 ( dd, + + + benzimidazol-5-yl) -2,4- 1 H, J = 2.3 and 8.8 Hz), 7.39 piri idindiamine (dd, 1H, J = 2.0 and 8.8 Hz), 7.04 (d, lH, J = 9.1 Hz), 3.76 (s, 3H). 1 H NMR (DMSO-d 6): d N 4 - (3,4-Dichlorophenyl) -5- 9.84 (s, 1 H), 9.70 (s, 1 H), fluoro-N 2 - (2- 8.19 (d, 1 H, J = 4.1 Hz), 8.05 801 trifluoromethyl-lH- (d, 1H, J = 2.3 Hz), 7.96 (s, + + + + benzimidazol-5-yl) -2.4- 1H), 7.75 (dd, 1H, J = 2.3 and pñrimidmdiamina 8.8 Hz), 7.60 (d, 1H, J = 9.1 Hz), 7.47-7.43 (, 2H). 1 H NMR (DMSO-d 6): d N 4 - (2,2-Dimethyl-3-oxo-10.71 (s, 1 H), 10.26 (s, 1 H), 4 H -benz [1,4] oxazin-6- 10.21 ( s, 1H), 8.22 (d, 1H, J il) -5-fluoro-N2- (2- = 4.9 Hz), 7.88 (s, 1H), 7.61 802 trifluoromethyl-lH- (d, 1H, J = 8.8 Hz), 7.49 (dd, + + + benzimidazol-5-yl) -2,4- 1 H, J = 2.3 and 8.8 Hz), 7.24 pyrimidindiamine (s, 1H), 7.22 (s, 1H), 6.86 (d, 1H, J = 8.8 Hz), 1.36 (s, 6H). 1 H NMR (DMSO-d 6): d 10.71 (s, 1 H), 10.27 (s, 1 H), (S) -5-Fluoro-N 4 - (2-10.22 (s, 1 H), 8.22 (d, 1 H, J methyl-3-oxo-2H, 4H- = 4.9 Hz), 7.93 (s, 1H), 7.62 benz [1,4] oxazin-6-yl) -803 (d, 1H, J = 8.8 Hz), 7.46 ( dd, N2- (2-trifluoromethyl-lH- + 1H, J = 2.3 and 8.8 Hz), 7.24 benzimidazol-5-yl) -2,4- (s, 1H), 7.21 (s, 1H), 6.89 (d , 1H, J = 8.8 Hz), 4.66 (qt, 1H, J = 6.7 Hz), 1.40 (d, 1H NMR (DMSO-d6): d 10.13 (s, 1H), 9.94 (s, 1H), N2- (3-Amino-l- 8.17 (d, 1H, J = 4.9 Hz), 7.76 methylindazol-5-yl) -N4- (s, 1H), 7.75 (d, 1H, J = 2.3 804 (3-chloro- 4-methoxyphenyl) - Hz), 7.61 (dd, 1H, J = 2.3 and + + 5-fluoro-2,4-9.1 Hz), 7.44 (s, 2H), 7.05 pirirm ^ indiamina (d, 1H, J = 9.1 Hz), 3.80 (s, 3H), 3.79 (s, 3H) .1H NMR (DMSO-d6): d 10.17 (s, 1H), 9.90 (s, VH), 8.21 (d, N2- (3- Amino-l- 1H, J = 4.7 Hz), 7.97 (d, lH, J = methylin-5-yl) -N4- 2.3 Hz), 7.90 (dd, lH, J = 2.3 and 805 (3,4-dichlorophenyl) ) -5- 8.8 Hz), 7.59 (d, 1H, J = 8.8 fluoro-2), 4- Hz), 7.47 (d, 1H, J = 8.8 Hz), pyrimdindiamine 7.38 (dd, 1H, J = 2.0 and 8.8 Hz), 4.41 (d, 2H, J = 6.7 Hz), 3.88 No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.75 (s, 1H), 10.46 (s) , 1H), N2- (3-Amino-l-10.40 (s, 1H), 8.22 (d, 1H, J = methylindazol-5-yl) -N4- 4.9 Hz), 7.79 (s, 1H), 7.54 ( 2,2-dimethyl-3-oxo-4H-806 (dd, 1H, J = 2.3 and 8.8 Hz), benz [1,4] oxazin-6-yl) -5- + 7.48 (d, 1H, J = 9.1 Hz), 7.28 fluoro-2,4- (app br s, 1H), 7.22 (dd, 1H, pyrinimediamine J = 2.3 and 9.1 Hz), 6.54 (d, 1H, J = 8.8 Hz), 3.84 (s, 1 H NMR (DMSO-d 6): d 10.76 (s, 1 H), 10.38 (s, 1 H), (S) -N 2 - (3-Amino-l-10.28 (s, 1 H), 8.20 (d, 1 H, J methylindazol-5-yl) -5- = 5.3 Hz), 7.80 (s, 1H), 7.53 fluoro-N4- (2-methyl-3-807 (d, 1H, J = 9.1 Hz), 7.48 (d, + oxo-4H- + 1H, J = 9.1 Hz), 7.27 (s, lH), benz [1,4] oxazin-6-yl) - 7.25 (s, 1H), 6.87 (d, 1H, J = 2, 4-? Irimidindiamine 9.1 Hz), 4.63 (qt, 1H, J = 6.7 Hz), 3.83 (s, 3H), 1.3 1 H NMR (DMSO-d6): d 9.53 (s, 1H), 9.40 (s, 1H), N4- (3-Chloro-4- 8.14 (d, 1H, J = 3.8 Hz), 8.13 methoxyphenyl) -5-fluoro- (s, 1H), 7.86 (d, 1H, J = 2.6 808 N2- (2-methyl-3H- + Hz), 7.72-7.67 (m, 2H ), 7.59 benzimidazol-5-yl) -2.4- (d, 1H, J = 8.8 Hz), 7.11 (d, pyrimidiamine 1H, J = 9.1 Hz), 3.83 (s, 3H), 2.72 (s, 3H) ). 1 H NMR (DMSO-d 6): d 9.93 (s, 2 H), 8.28 (d, 1 H, J = N 4 - (3,4-dichlorophenyl) -5- 4.8 Hz), 8.12 (d, 1 H, J = 2.6 fluoro -N2- (2-methyl-3H-809 Hz), 8.07 (s, 1H), 7.81 (dd, benzimidazol-5-yl) -2,4- + + 1H, J = 2.3 and 9.1 Hz), 7.66 piri idindiainin (s, 2H), 7.56 (d, 1H, J = 8.8 Hz), 2.75 (s, 3H). 1 H NMR (DMSO-d 6): d 10.70 (s, 1 H), 9.56 (s, 1 H), 9.40 (s, N 4 - (2,2-Dimethyl-3-oxo-1 H), 8.21 (s, 1 H), 8.12 (d, lH, J 4H-benz [1,4] oxazin-6- = 3.8 Hz), 7.79 (dd, 1H, J = 2.3 810 il) -5-fluoro-N2- (2-methyl- + y 9.1 Hz), 7.55 (d, 1H, J = 8.8 3H-benzimidazol-5-yl) - Hz), 7.52 (s, 1H), 7.31 (dd, 1H, 2,4-? Irimidmdiamine J = 2.3 and 8.8 Hz ), 6.88 (d, 1H, J = 8.8 Hz), 2.72 (s, 3H), l. 1 H NMR (DMSO-d 6): d 10.69 (S) -5-Fluoro-N 2 - (2- (s, 1H), 9.58 (s, 1H), 9.42 (s, methyl-3H-benzimidazole-1H), 8.23 (s, 1 H), 8.12 (d, 1 H, J 5-yl) -N 4 - (2-methyl-3-oxo- = 3.5 Hz), 7.74 (dd, 1 H, J = 2.3 811 2 H, 4 H -benz [ 1, 4] oxazin- and 8.8 Hz), 7.57 (d, 1H, J = 9.1 6-yl) -2.4-Hz), 7.53 (d, 1H, J = 2.3 Hz), pyr aidindiamiaa 7.29 (dd, lH, J = 2.3 and 8.8 Hz), 6.91 (d, lH, J = 8.8 Hz), 4.64 No. Name of Compound Physical Data Tftase Triptase Tftasa f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE , 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 11.06 (s, 1H), 9.53 (s, 1H), N2- (1, 3-dimethylindazole- 9.44 (s, 1H), 8.16 (d , 1H, J = 6-yl) -N4- (2,2-dimethyl-3- 3.5 Hz), 7.83 (s, 1H), 7.53 oxo-4H-5-812 (d, 1H, J = 8.5 Hz) , 7.45 (d,? Irid [1,4] oxazin-6-yl) -5- 1 H, J = 8.8 Hz), 7.30 (d, lH, fluoro-2,4-J = 8.5 Hz), 7.15 (dd) , 1H, J = pyrimidinediamine 2.3 and 8.8 Hz), 3.67 (s, 3H), 2.33 (s, 3H), 1.36 (s, 6H 1H NMR (DMSO-d6): d 12.21 (s, 1H), 11.02 (s) , 1H), N4- (2,2-Dimethyl-3-oxo- 9.30 (s, 1H), 9.12 (s, 1H), 4H-5-pyrid [1,4] oxazin-8.11 (d, 1H, J = 3.5 Hz), 7.90 813 6-yl) -5-fluoro-N2- (3- (s, 1H), 7.69 (d, 1H, J = 8.5 + methyl-lH-indazol-6-yl) - Hz), 7.43 (d, lH, J = 8.5 Hz), 2,4-phenylene diamine 7.33 (d, 1H, J = 8.8 Hz), 7.19 (d, 1H, J = 8.8 Hz), 2.34 (s, 3H), 1.36 (s, 6H). 1 H NMR (DMSO-d 6): d 11.10 (s, 1 H), 9.22 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo- 9.19 (s, 1 H), 8.12 (d, 1 H, J = 4H-5-? Irid [1,4] oxazin- 3.5 Hz), 8.05 (s, 1H), 7.84 (s, 814 6-yl) -5-fluoro-N2- [l- (3-1H), 7.57 (d, lH, J = 8.5 Hz), + methoxypropyl) indazole-5- 7.50 (d, 1H, J = 8.8 Hz), 7.46 yl] -2.4-? Inum ^ indiamine (d, 1H, J = 8.8 Hz), 7.35 (d, 1H, J = 8.8 Hz), 4.37 (t, 2H, J = 6.4 Hz), 3.22 (t, 1H NMR (DMSO-d6): d N4- (3-Chloro-4-) 10.36 (s, 1H), 10.25 (s, 1H), 8.21 (d, 1H, J = 4.9 Hz), 7.85 methoxyphenyl) -5-fluoro- (s, 1H), 7.79-7.75 (m, 5H), N2 - [l- [3- (N- 815 7.67 (d, 1H, J = 2.3 Hz), 7.63 + jfelimidopropyl)] indazole- (d, 1H, J = 8.8 Hz), 7.49 (dd, 5-yl) - 2,4- 1H, J = 2.3 and 8.8 Hz), 7.32 pyrimidinediamine (dd), 1H, J = 1.8 and 9.1 Hz), 7.03 (d, lH, J = 8.8 Hz) 1H NMR (DMSO-d6): d 10.24 (s, lH), 9.99 (s, 1H), N4- (3, 4-Dichlorophenyl) -5- 8.23 (d, 1H, J = 4.7 Hz), 7.95 fluoro-N2- [l- [3- (N- (d, 1H, J = 2.0 Hz), 7.87 (s, 16 ñalimidopropyl )] indazole-1H), 7.80 (s, 1H), 7.78-7.73 5-il] -2.4- (m, 4H), 7.64 (d, lH, J = 9.1 pyrimidinediainine Hz), 7.45 (d, 1H) , J = 8.8 Hz), 7.36 (dd, 1H, J = 1.8 and 9.1 Hz), 4.41 (t, 2H, J = 6.7 No. Compound Name Physical Data Triptase Tftase Triptase f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N4- (2,2-Dimethyl-3-oxo- 10.78 (s, 1H), 10.45 (s, 1H) , 4H-benz [1,4] oxazin-6- 10.32 (s, 1H), 8.24 (d, 1H, J il) -5-fluoro-N2- [l- [3- = 4.9 Hz), 7.88 (s) , 1H), 7.87-817 (N- (s, 1H), 7.84-7.77 (m, 4H), + ñalimidopropyl)] indazole- 7.65 (d, 1H, J = 8.8 Hz), 7.37 5-il] -2, 4- (dd, 1H, J = 1.8 and 9.1 Hz), pyrimidinediamine 7.20 (d, 1H, J = 8.8 Hz), 6.86 (d, 1H, J = 9.1 Hz), 4.4 1 H NMR (DMSO-d6): d (S) -5-Fluoro-N4- (2- 10.80 (s, 1H) , 10.44 (s, 1H), methyl-3-oxo-2H, 4H-10.30 (s, 1H), 8.24 (d, 1H, J benz [1,4] oxazin-6-yl) - = 5.3 Hz), 7.89 (s, 1H), 7.87 818 N2- [l- [3- (N- (s, 1H), 7.82-7.77 (, 4H), phthalophenpropyl-jindazole-7.67 (d, 1H, J = 8.8 Hz), 7.37 5-yl] -2,4- (dd, 1H, J = 1.8 and 9.1 Hz), pyrimidmdiamine 7.22 (dd, 1H, J = 1.8 and 8.8 Hz), 7.18 (s, 1H), 6.89 (d 1H NMR (DMSO-d6): d 10.22 (s, 1H), 10.05 (s, 1H), N2- [l- [3- (N- 8.21 (d, 1H, J = 4.9 Hz), 7.92 Acetylamino) propyl] inda (s, 1H), 7.90 (m, 1H), 7.86 819 zol-5-yl] -N4- (3-chloro-4- (s, 1H), 7.75 (d, 1H, J = 2.3 + + methoxyphenyl) -5-fluoro-Hz), 7.64 (d, 1H, J = 9.1 Hz), 2,4-? Irimidindiamine 7.57 (dd, 1H, J = 2.3 and 8.8 Hz), 7.39 (dd, 1H, J = 1.8 and 8.8 Hz), 7.09 (d, 1H, J 1 H NMR (DMSO-d 6): d 9.51 (s, 1H), 9.23 (s, 1), 8.10 N2- [l- [3- (N- (d, 1H , J = 3.8 Hz), 8.04 (d, Acetylamino) propi] inda 1H, J = 2.3 Hz), 7.95 (s, lH), 820 zol-5-yl] -N4- (3,4-7.82 (m, 2H), 7.74 (dd, 1H, J dichlorophenyl) -5-fluoro- = 2.0 and 9.1 Hz), 7.51 (d, 1H, 2,4-pyrirm ^ mdiamine J = 9.1 Hz), 7.44 (d, 1H, J = 9.1 Hz), 7.43 (dd, 1H, J = 1.8 and 9.1 Hz), 4.30 (1H NMR (DMSO-d6): d N2- [l- [3- ( N- 10.77 (s, 1H), 10.38 (s, 1H), Acetylamino) propyl] inda 10.18 (s, 1H), 8.21 (d, 1H, J zol-5-yl) -N4- (2,2- = 4.9 Hz), 7.90 (s, 3H), 7.61 21 dimethyl-3-oxo-4H- (d, 1H, J = 8.8 Hz), 7.36 (dd, + benz [1,4] oxazin-6-yl) - 5-1H, J = 2.0 and 9.1 Hz), 7.21 fluoro-2,4- (d, 1H, J = 8.5 Hz), 7.18 (s, pyrimidinediamine 1H), 6.89 (d, lH, J = 8.5 Hz), 4.36 (t, 2H, J = 7.0 Hz No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com ID, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6 ): d N2- [l- [3- (N- 11.05 (s, 1H), 9.18 (s, 1H), Acetylamino)? ropi] - 9.15 (s, 1H), 8.07 (d, 1H), indazole- 5-ü] -N4- (2.2- 3.5 Hz), 8.01 (s, 1H), 7.80 822 dimethyl-3-oxo-4H-5- (d, 1H, J = 6.3 Hz), 7.79 (s, + pyridfl, 4] oxazin-6-yl) -5- 1 H), 7.52 (d, 1H, J = 8.5 Hz), fluoro-2,4-7,47-7,40 (m, 2H), 7.31 (d, pyrimidinediamine 1H , J = 8.5 Hz), 4.29 (t, 2H, J = 7.0 Hz), 2.94 (qt, 2H, J = 1H NMR (DMSO-d6): d 10.25 (s, 1H), 10.21 (s, 1H), N2- [l- (3- 8.21 (d, 1H, J = 4.8 Hz), 7.97 Aminopropyl) indazole-5- (br s, 2H), 7.88 (s, 1H), 7.84-823 il] -N4- (3-chloro-4-7.78 (m, 2H), 7.70 (d, 1H, J + methoxyphenyl) -5-fluoro- = 2.6 Hz), 9.08 (d, 1H, J = 2,4-? irithmidinediamine 9.1 Hz), 7.49 (dd, 1H, J = 2.6 and 8.8 Hz), 7.36 (dd, 1H , J = 1.8 and 8.8 Hz), 7.06 (d 1 H NMR (DMSO-d 6): d 10.01 (s, 1H), 9.77 (s, 1H), N2- [l- (3- 8.24 (d, 1H, J = 3.1 Hz), 8.06 Aminopropyl) indazole-5- (d, 1H, J = 2.6 Hz), 7.96 (s, 824 il] -N4- (3,4- 1H), 7.95 (s, 1H), 7.90- 7.85 dichlorophenyl) -5-fluoro- (m, 2H), 7.75 (d, lH, J = 8.5 2,4-? Irimidindiamine Hz), 7.67 (d, lH, J = 8.8 Hz), 7.53 (d, 1H, J = 8.8 Hz), 7.47 (dd, lH, J = 2.0 and 9.1 1 H NMR (DMSO-d6): d N2 -_ [l- (3- 10.77 (s, 1H), 10.35 (s, 2H), Aminopropyl ) indazol-5- 8.20 (d, lH, J = 5.0 Hz), 7.94 il] -N4- (2,2-dimethyl-3- (br s, 2H), 7.94 (s, 1H), 7.86 825 oxo- 4H- (s, 1H), 7.82-7.79 (m, 1H), benz [1,4] oxazin-6-yl) -5- 7.62 (d, 1H, J = 9.1 Hz ), 7.34 fluoro-2, 4- (dd, 1H, J = 1.8 and 9.1 Hz), pyrimidinediamine 7.21 (br s, 1H), 7.15 (dd, lH, J = 1.8 and 8.8 Hz), 1H NMR (DMSO-d6): d 10.78 ( s, 1H), 10.30 (s, 2H), (S) -N2- [l- (3- 8.18 (d, 1H, J = 4.9 Hz), 7.93 Aminopropyl) indazole-5- (br s, 2H), 7.91 (s, 1H), 7.87 il] -5-fluoro-N4- (2-methyl-826 (s, 1H), 7.83-7.80 (m, 1H), + 3-oxo-2H, 4H- 7.63 (d , 1H, J = 8.8 Hz), 7.36 benzfl, 4Joxazin-6-yl) - (dd, 1H, J = 1.8 and 8.8 Hz), 2,4-pyrimidinediamine 7.21 (br s, 1H), 7.17 (dd, lH , J = 2.3 and 8.5 Hz), No. Name of Compound Physical Data Triptase Triptase Tftasa f_syk Com LD, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6) : d 10.39 (s, 1H), 10.03 (s, 1H), Salt of Acid p- 8.20 (d, 1H, J = 5.3 Hz), 7.95 toluenesulfonic of N4- (s, 1H), 7.80 (d, lH, J = 1.8 (3-Chloro-4-methoxyphenyl) - 827 Hz), 7.74 (d, lH, J = 2.6 Hz), + 5-fluoro-N2- [l- (3- 7.64 (d, 1H, J = 8.8 Hz), 7.54 hydroxypropyl) indazole-5- (dd, 1H, J = 2.6 and 9.1 Hz), ü] -2,4-pyrimidine diamine 7.46 (d, 2H, J = 8.1Hz), 7.38 (dd, lH, J = 2.1y 1H NMR (DMSO-d6): d Acid Salt p-10.63 (s, 1H), 10.23 (s, 1H), toluene sulfonic Bis of 8.24 (d, 1H, J = 5.5 Hz), 7.97 N4- (3-Chloro-4- (s, 1H), 7.76 (d, 1H, J = 1.8 828 methoxyphenyl) -5-fluoro-Hz), 7.72 (d, 1H, J = 2.4 Hz), + N2- [l- (3- 7.66 (d, 1H, J = 9.1Hz), 7.52 hydroxypropyl) indazole-5- (dd, 1H, J = 2.6 and 8.8 Hz), H] -2,4-? irimidindiamine 7.47 (d , 4H, J = 8.1Hz), 7.35 (dd, lH, J = 1.8y 1H NMR (DMSO-d6): d 10.38 (s, 1H), 10.02 (s, 1H), Salt of Acid 8.19 (d, 1H , J = 4.7 Hz), 7.95 benzenesulfonic of N4- (s, 1H), 7.80 (s, 1H), 7.74 (s, (3-Chloro-4-methoxyfenu) - 829 1H), 7.65-7.58 (m, 4H ), 7.38 5-fluoro-N2- [l- (3- + (d, 1H, J = 9.1 Hz), 7.29 (s, hydroxypropyl) indazol-5- 3H), 7.07 (d, lH, J = 8.8 Hz ), il] -2,4-? irimidindiamine 4.42 (t, 2H, J = 6.7 Hz), 3.82 (s, 3H), 3.37 (t, 2H, 1H NMR (DMSO-d6): d Acid 10.29 ( s, 1H), 9.95 (s, 1H), Bencenesulfonic Bis of 8! 9 (d, 1H, J = 5.1Hz), 7.94 N4- (3-Chloro-4- (s, 1H), 7.81 (d, 1H , J = 1.8 830 methoxyphenyl) -5-fluoro-Hz), 7.7 5 (d, lH, J = 2.6 Hz), + N2- [l- (3- 7.65-7.53 (, 7H), 7.39 (dd, Mdroxypropyl) indazol-5-1H, J = 2.0 and 8.8 Hz), 7.31 - ñ] -2,4-pyrj ™ dindiamine 7.26 (m, 5H), 7.07 (d, 1H, J = 8.8 Hz), 4.42 (t, 2H, J 1H NMR (DMSO-d6): d 10.36 (s, 1H), 10.25 (s, 1H), Chloride Salt of 8.21 (d, 1H, J = 5.3 Hz), 7.87 Hydrogen of N4- (3- (s, 1H), 7.77 (d, 1H, J = 1.5 Chlorine -4-methoxyphenyl) -5-31 Hz), 7.69 (d, lH, J = 2.1Hz), + fluoro-N2- [l- (3- 7.57 (d, lH, J = 9.1Hz), 7.49 hydroxy? ropil) indazol-5- (dd, 1H, J = 2.3 and 8.8 Hz), ü] -2,4-pyrimidiamine 7.33 (dd, 1H, J = 2.0 and 9.1 Hz), 7.03 (d, 1H, J = No Name of Compound Physical Data Tftase Tftase Triptase f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 10.60 (s, 1H ), 10.52 (s, 1H), N4- (3-Chloro-4- 8.30 (d, 1H, J = 5.6 Hz), 7.95 methoxyphenyl) -5-fluoro- (s, 1H), 7.81 (d, 1H, J = 1.8 N2- [l- [3- (N- 832 Hz), 7.73 (d, lH, J = 2.3 Hz), + + methylsulfonnarnino) - 7.69 (d, lH, J = 9.1 Hz), 7.52 propyl] indazol-5-il] -2, 4- (dd, 1H, J = 2.3 and 8.8 Hz), pyrimidinediamine 7.37 (dd, 1H, J = 2.0 and 8.8 Hz), 7.10 (br s, 1H), 7 1H NMR (DMSOdβ): d 9.53 (s, 1H), 9.25 (s, 1H), N4- (3,4-Dichlorophenyl) -5-8.11 (d, 1H, J = 3.8 Hz), 8.04 fluoro-N2- [l- [3- (N- (d , 1H, J = 2.3 Hz), 7.97 (br 833 methylsulfonylamino) -s, 1H), 7.83 (s, 1H), 7.73 (d, + propyl] indazol-5-yl] -2,4- 1H, J = 2.3 and 8.8 Hz), 7.53 pyrir dindiamine (d, 1H, J = 8.8 Hz), 7.44 (d, 1H, J = 8.8 Hz), 7.43 (dd, lH, J = 2.3 and 8.8 Hz), 7.0 1H NMR ( DMSO-d6): d 10.74 (s, 1H), 10.24 (s, 1H),, N4- (2,2-Dimethyl-3-oxo- 9.98 (s, 1H), 8.2 l (d, 1H, J = 4H-benz [1,4] oxazin-6- 4.3 Hz), 7.93 (s, 1H), 7.90 (s, ü) -5-fluoro-N2- [l- [3- 834 1H), 7.61 (d, lH, J = 8.8 Hz), (N-methylsulfonylamino) -7.38 (dd, 1H, J = 1.8 and 9.1 propyl] indazol-5-yl] -2.4-Hz), 7.22 (dd, 1H, J = 1.8 and pirinridindiamine 8.8 Hz), 7.17 (s, 1H), 7.09 (app t, 1H, J = 5.3 1H NMR (DMSO-d6): d (S) -5-Fluoro-N4- (2- 10.80 (s, 1H ), 10.42 (s, 1H), methyl-3-oxo-2H, 4H-10.25 (s, 1H), 9.98 (s, 1H), benz [1,4] oxazin-6-yl) - 8.22 (d, 1H, J = 4.9 Hz), 7.92 835 N2- [l- (3- (N- (s, 1H), 7.90 (d, 1H, J = 1.5 + + methylsulfonamino) - Hz), 7.64 (d, lH , J = 8.8 Hz), 11. 11 (s, 1H), 9.25 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.24 (s, 1H), 8.11 (d, 1H, J = 4H-5-pyrid [1, 4] oxazin- 3.0 Hz), 8.07 (s, 1H), 7.85 (s, 6-yl) -5-fluoro-N2- [l- [3- 836 1 H), 7.58 (d, lH, J = 8.5 Hz ), + (N-methylsulfonylamino) - + 7.54 (d, lH, J = 9.1 Hz), 7.48? Rophilic] indazol-5-yl] -2,4- (d, 1H, J = 9.1 Hz), 7.36 ( d, pyrimidinediamine 1H, J = 8.5 Hz), 7.06 (t, 1H, J = 6.7 Hz), 4.39 (t, No. Name of Compound Physical Data Tftase Triptase Triptase f syk Com LD, LD, ID, llpt CMC, CMC , CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- (3-Amino-l-11.17 (s, 1H), 10.22 (s, 1H), methylindazol-5-yl) -N4- 10.13 (s, 1H), 8.25 (d, 1H, J (2,2-dimethyl-3-oxo-4H- = 4.4 Hz), 7.92 (s, 1H), 7.58 837 5-pyrid [l, 4] oxazin-6-yl) - + (d, 1H, J = 9.1 Hz), 7.50 (d, + 5-fluoro-2,4-1H, J = 9.1 Hz), 7.34 (d, 1H, pyrimidinediamine J = 8.5 Hz), 3.86 (s, 3H), 1.39 (s, 3H) .1H NMR (DMSO-d6): d 11.22 (s, 1H), 10.22 (s, 1H), N4- (2,2-Dimethyl) -3-oxo-10.09 (s, 1H), 8.25 (d, 1H, J 4H-5-pyrid [1,4] oxa zin- = 4.4 Hz), 7.90 (s, 2H), 7.57 838 6-ü) -5-fluoro-N2- [l- (3- (d, 1H, J = 9.3 Hz), 7.41- + hydroxypropyl ) indazol-5- 7.35 (m, 3H), 4.40 (t, 2H, J = ü] -2,4-pyrimidinediamine 6.7 Hz), 3.35 (t, 2H, J = 6.4 Hz), 1.93 (app q, 2H , J = 6.7 Hz), 1.40 (s, 6H). 1 H NMR (DMSO-d 6): d 11.10 (s, 1 H), 9.46 (s, 1 H), N 4 - (2,2-Dimethyl-3-oxo-9.27 (s, 1 H), 8.19 (d, 1 H, J = 4H-5-pyrid [1,4] oxazin- 3.5 Hz), 8.01 (s, 1H), 7.87 (s, 839 6-yl) -5-fluoro-N2- [l- (3-1H), 7.65 (d, 1H, J = 8.5 Hz), + methoxypropyl) indazole-6- 7.54 (d, 1H, J = 8.8 Hz), 7.35 ü] -2,4-pyrimidine diamine (d, 1H, J = 8.5 Hz ), 7.29 (d, 1H, J = 8.8 Hz), 4.19 (t, 2H, J = 6.7 Hz), 3.16 (t, 1H NMR (DMSO-d6): d 9.47 (br s, 1H), 9.28 (s) , 1H), N4- (3-Chloro-4-9.17 (s, 1H), 8.07 (d, 1H, J = methoxyphenyl) -5-fluoro- 3.8 Hz), 8.04 (s, 1H), 7.84 (s, N2- [l- [3- (N- 40 1H), 7.79 (d, 1H, J = 2.6 Hz), trifluoromethylsulfonyl- + 7.64 (dd, 1H, J = 2.3 and 9.1 amino) propyl] indazole-5 Hz ), 7.52 (d, 1H, J = 8.8 Hz), ü] -2,4-pyriridinediamine 7.49 (d, lH, J = 9.1 Hz), 7.07 (d, 1H, J = 8.8 H 1 H NMR (DMSO-d6) ): d 10.48 (s, 1H), 10.28 (s, 1H), N4- (3,4-Dichlorophenyl) -5- 9.55 (t, 1H, J = 5.2 Hz), 8.32 fluoro-N2- [l- [ 3- (N- (d, 1H, J = 4.9 Hz), 8.00 (d, 41 trifluoromethylsulfonyl- 1H, J = 2.0 Hz), 7.98 (s, lH) , + amino) propu] indazol-5- 7.85-7.81 (m, 1H), 7.70-7.65 il] -2,4-? irirmdmdiamine (m, 2H), 7.52 (d, lH, J = 8.8 Hz), 7.42 (dd, 1H, J = 2.0 and 9.1 Hz), 4.45 (t, 2H, No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1 H NMR (DMSO-d 6): d N 4 - (2,2-Dimethyl-3-oxo-10.63 (s, 1H), 9.46 (br s, 4H-benz [1,4] oxazin-6 1H), 9.28 (s, 1H), 9.06 (s, ü) -5-fluoro-N2- [l- [3-1H), 8.12 (s, 1H), 8.05 (d, 842 (N- lH, J = 3.8 Hz), 7.80 (s, 1H), + trifluoromethylsulfonyl- 7.47 (app d, 2H, J = 9.1 Hz), amino) propyl] indazol-5- 7.29 (dd, 1H, J = 2.0 and 8.8 ü) - 2,4-pyrimidinediamine Hz), 7.20 (d, lH, J = 2.0 Hz), 6.89 (d, 1H, J = 8.8 Hz), 4.37 1 H NMR (DMSO-d6): d (S) -5-Fluoro- N4- (2- 10.74 (s, 1H), 9.88 (s, 1H), methyl-3-oxo-2H, 4H- 9.68 (s, 1H), 9.49 (t, 1H, J = benz [l, 4] oxazin-6-yl) - 6.7 Hz), 8.13 (d, 1H, J = 4.7 843 N2- [l- [3- (N-Hz), 8.01 (s, 1H), 7.87 (s, + trifluoromethylsulfonyl- 1H ), 7.56 (d, lH, J = 9.1 Hz) , amino) pro? il] indazol-5- 7.43 (d, lH, J = 9.1 Hz), 7.26 ü] -2,4-? ptmidindiamine (d, 1H, J = 8.5 Hz), 7.21 (s, 1H) , 6.90 (d, 1H, J = 8.5 1 H NMR (DMSO-d 6): d N 4 - (2,2-Dymmethyl-3-oxo- 11.10 (s, 1H), 9.46 (br s, 4H-5-? Irid [1,4] oxazin-1H), 9.23 (s, 1H), 9.19 (s, 6-yl) -5-fluoro-N2- [l- [3-1H), 8.11 (dd, 1H, J = 0.9 and 844 (N- 3.5 Hz), 8.07 (s, 1H), 7.86 (s, trifluoromethylsulfonyl- 1H), 7.59 (d, 1H, J = 8.5 Hz), arr? ino) propyl] indazol-5 - 7.53 (d) , 1H, J = 9.1 Hz), il] -2,4-? Irimi? Niandiamine 7.49 (d, 1H, J = 8.8 Hz), 7.35 (d, 1H, J = 8.5 Hz), 4.39 (t, 1H NMR (DMSO-d6): d 11.11 (s, 1H), 9.68 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.42 (s, 1H), 8.20 (d, 1H, J = 4H -5-? Irid [1, 4] oxazin- 3.5 Hz), 8.13 (s, 1H), 7.73 6-yl) -5-fluoro-N2- (2-845 (dd, 1H, J = 1.8 and 9.1 Hz), methyl-3H-benzimidazole- + + 7.63 (d, 1H, J = 8.5 Hz), 7.57 5-il) -2,4- (d, 1H, J = 9.1 Hz) , 7.39 (d, pyrimidindiamine 1H, J = 8.5 Hz), 2.73 (s, 3H), 1.42 (s, 6H). 1 H NMR (Dd 6): d 13.56 (br s 1 H), 11.07 (s, N 4 - (2,2-Dimethyl-3-oxo-1 H), 9.43 (s, 1 H), 9.20 (s, 4 H-5 -pyrid [1,4] oxazin-1H), 8.16 (d, 1H, J = 3.5 Hz), 6-yl) -5-fluoro-N2- (2- 8.13 (s, 1H), 7.73 (dd, 1H , J trifluoromethyl-lH- + + + benzimidazol-5-yl) -2,4- = 1.8 and 9.1 Hz), 7.61 (d, 1H, J = 8.5 Hz), 7.55 (d, 1H, J = pyrimidinediamine 9.1 Hz ), 7.36 (d, 1H, J = 8.5 Hz), 1.42 (s, 6H).

No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 9.27 (s, 1H), 9.16 (s, 1H), N4- (3-Chloro-4- 8.07 (d, 1H, J = 3.5 Hz), 8.03 methoxyphenyl) -N2- [l- (3- (s, 1H), 7.82 (s, 1H), 7.79 (d, (diethylphosphonamido) -847 1H, J = 2.3 Hz), 7.65 (dd, pro? il] indazol-5-yl] -5- + 1H, J = 2.3 and 8.5 Hz) , 7.53 fluoro-2,4- (d, 1H, J = 8.5 Hz), 7.47 (d, pyrimidineamine 1H, J = 9.1 Hz), 7.08 (d, 1H, J = 9.1 Hz), 4.91 (dt, 1H, 1 H NMR (DMSO-d 6): d 10.42 (s, 1 H), 10.29 (s, 1 H), N 4 - (3-Chloro-4- 8.26 (d, 1 H, J = 4.9 Hz), 7.93 methoxyphenyl) -5- fluoro- (s, 1H), 7.83 (s, 1H), 7.74 (s, N2- [l- (3-1H), 7.62 (d, lH, J = 8.8 Hz), pivalamidopropyl) - + 7.55-7.47 ( m, 2H), 7.39 (d, indazol-5-yl) -2.4- 1H, J = 9.1 Hz), 7.09 (d, 1H, pyrimidiamine J = 8.8 Hz), 4.35 (t, 2H, J = 7.0 Hz), 3.82 (s, 3H), 1H NMR (DMSO-d6): d 9.55 (s, 1H), 9.28 (s, 1H), N4- (3,4-Dichlorophenyl) -5- 8.15 (dd, 1H , J = 1.2 and 3.7 fluoro -N2- [l- (3- Hz), 8.09 (d, lH, J = 1.5 Hz), 849 pivalamidopropyl) -8.00 (s, 1H), 7.87 (s, 1H), + indazol-5-yl] - 2.4- 7.79 (dd, 1H, J = 1.8 and 9.1 pirin? Dmdiamine Hz), 7.54-7.44 (m, 4H), 4.33 (t, 2H, J = 6.7 Hz), 3.04 (qt, 2H, J = 6.4 Hz), 1.94 (app 1H NMR (DMSO-d6): d 10.74 (s, 1H), 10.21 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.89 (s, 1H) , 8.18 (d, 1H, J = 4H-benz [1,4] oxazin-6- 4.4 Hz), 7.93 (s, 1H), 7.88 (s, il) -5-fluoro-N2- [l- (3 - 850 1H), 7.56 (d, lH, J = 8.5 Hz), pivalamidopropyl) - + 7.46 (t, 1H, J = 5.6 Hz), 7.37 indazol-5-yl] -2,4- (d, 1H, J = 9.1 Hz), 7.23 (d, pyrimidindiamine 1H, J = 9.1 Hz), 7.17 (s, lH), 6.88 (d, 1H, J = 8. 1H NMR (DMSO-d6): d 5-Fluoro- ( S) -N4- (2- 10.80 (s, 1H), 10.42 (s, 1H), methyl-3-oxo-4H-10.28 (s, 1H), 8.22 (d, 1H, J benz [1, 4] oxazin-6-yl) - = 4.4 Hz), 7.90 (s, 2H), 7.59 51 N2- [l- (3- (d, 1H, J = 8.8 Hz), 7.47 (m, + pivalamidopropyl) - 1H) , 7.38 (d, 1H, J = 8.8 Hz), indazol-5-yl] -2.4-7.22 (app d, 2H, J = 8.8 Hz), pyrimidinediamine 6.91 (d, 1H, J = 8.8 Hz), 4.64 (qt, lH, J = 6.7 Hz), 4 No. Compound Name Physical Data Triptase Tftase Triptase f syk Com LD, ID, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 11.10 (s, 1H), 9.22 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.18 (s, 1H), 8.12 (d, 1H, J = 4H-5-? irido [1,4] oxazin- 3.5 Hz), 7.84 (s, 1H), 7.82 (s, 6-yl) -5-fluoro-N2- [l- ( 3-852 1H), 7.59 (d, lH, J = 8.8 Hz), + pivalamidopropyl) - 7.48-7.43 (m, 3H), 7.36 (d, indazol-5-yl] -2,4- 1H, J = 8.5 Hz), 4.32 (t, 2H, pyrirm ^ mdiamine J = 6.7 Hz), 3.02 (qt, 2H, J = 6.7 Hz), 1.92 (app q, 2 1 H NMR (DMSO-d6): d 9.28 (s, 1H), 9.17 (s, 1H), N4- (3-Chloro-4- 8.07 (d, 1H, J = 3.5 Hz), 7.82 methoxyphenyl) -5-fluoro- (s, 1H), 7.78 (d, 1H , J = 2.0 N2- [l- [3- (N- 853 Hz), 7.66 (dd, 1H, J = 2.0 and succinimidopropyl)] - + + 8.5 Hz), 7.52 (d, 1H, J = 9.1 indazole- 5-yl] -2.4-Hz), 7.46 (d, lH, J = 9.1 Hz), pyrii dindiamine 7.09 (d, 1H, J = 8.5 Hz), 4.33 (t, 2H, J = 6.3 Hz), 3. 1 H NMR (DMSO-d 6): d 9.55 (s, 1H), 9.28 (s, 1H), N4- (3,4-Dichlorophenyl) -5- 8.16 (d, 1H, J = 3.5 Hz), 8.08 fluoro-N2- [l- [3- (N- (d, 1H, J = 2.3 Hz ), 8.01 (s, 854 succinimidopropyl)] - 1H), 7.88 (s, 1H), 7.80 (dd, indazol-5-yl] -2,4- 1H, J = 2.3 and 8.8 Hz), 7.56 pyrimidiamine (d) , 1H, J = 8.8 Hz), 7.51-7.46 (m, 2H), 4.35 (t, 2H, J = 6.7 Hz), 3.40 (t, 2H, J = 7.0 1H NMR (DMSO-d6): d 10.73 ( s, 1H), 10.38 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 10.25 (s, 1H), 8.18 (d, 1H, J 4H-benz [1,4] oxazin-6 - = 3.9 Hz), 7.85 (s, 1H), 7.83 il) -5-fluoro-N2- [l- [3-855 (s, 1H), 7.56 (d, lH, J = 9.1 (N-succinimidopropyl) ] - + + indazol-5-yl] -2,4-Hz), 7.32 (d, lH, J = 8.8 Hz), 7.14 (d, 2H, J = 9.1 Hz), 6.84 pyrimidiamine (d, 1H, J = 8.8 Hz), 4.30 (t, 2H, J = 7.0 Hz), 3.34 (t 1H NMR (DMSO-d6): d (S) -5-Fluoro-N4- (2- 10.82 (s, 1H), 10.52 (s, 1H), methyl-3-oxo-2H, 4H-10.42 (s, 1H), 8.24 (d, 1H, J-benz [1,4] -oxazin-6-yl) - = 4.9 Hz), 7.92 ( s, 1H), 7.87 56 N2- [l- [3- (N- (s, 1H), 7.63 (d, lH, J = 8.8 succinimidopropyl)] - Hz), 7.37 (dd, 1H, J = 1.0 yindazol-5-il] -2, 4-8.8 Hz), 7.20 (d, 2H, J = 8.8 pyrjimidinediamine Hz), 6.91 (d, lH, J = 9.1 Hz), 4.65 (qt, 1H, J = 6.7 Hz No. Compound Name Physical Data Triptase Triplase Triptase f_syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 11.10 (s, 1H), 9.23 (s, 1H), N4 - (2,2-Dimethyl-3-oxo- 9.19 (s, 1H), 8.12 (d, 1H, J = 4H-5-pyrid [1,4] oxazin- 3.5 Hz), 8.06 (s, 1H), 7.57 6-yl) -5-fluoro-N2- [l- [3- (d, 1H, J = 8.8 Hz), 7.53-857 + (N-succinimidopro? Il)] - 7.46 (m, 2H), 7.36 (d, 1H, J indazol-5-yl] -2.4- = 8.8 Hz), 4.33 (t, 2H, J = pyriniidinediamine 7.0 Hz), 3.39 (t, 2H, J = 6.7 Hz), 2.54 (s) , 2H), 2.48 (s, 2H), 2 1 H NMR (DMSO-d 6): d 10.26 (s, 1H), 10.08 (s, 1H), N4- (3-Chloro-4- 8.22 (d, 1H, J = 4.3 Hz), 7.92 methoxyphenyl) -N2- [l- [3- (s, 1H), 7.85 (s, 1H), 7.74 (2.6-858 (d, lH, J = 2.0 Hz), 7.62 (d, dioxopi? eridino] propyl) - + 1H, J = 8.8 Hz), 7.57 (dd, indazol-5-yl] -5-fluoro- 1H, J = 2.3 and 8.8 Hz), 7.39 2.4-pyri ? ^ indiamina (dd, 1H, J = 2.0 and 8.3 Hz ), 7.09 (d, 1H, J = 8.8 Hz), 4.35 1 H NMR (DMSO-d 6): d 10.05 (s, 1H), 9.77 (s, lh), N 4 - (3,4-Dichlorophenyl) - 8.23 ( d, lH, J = 5.1 Hz), 8.03 N2- [l- [3- (2,6- (s, 1H), 7.92 (s, 1H), 7.91 (s, 859 dioxopiperidino) propyl] - 1H), 7.73 (d, lH, J = 8.8 Hz), + indazol-5-yl] -5-fluoro- 7.61 (d, 1H, J = 8.8 Hz), 7.51 2,4-pyrinidinediamine (d, lH, J = 8.8 Hz), 7.44 (d, 1H, J = 8.8 Hz), 4.35 (t, 2H, J = 6.7 Hz), 3.67 (t, 2 1H NMR (DMSO-d6): d 10.76 (s, 1H), 10.34 ( s, 1 H), N 4 - (2,2-Dimethyl-3-oxo-10.16 (s, 1 H), 8.21 (d, 1 H, J 4 H -benz [1,4] oxazin-6- = 4.3 Hz), 7.89 (s, 2H), 7.59 il) -N2- [l- [3- (2,6- 860 (d, 1H, J = 8.5 Hz), 7.37 (dd, dioxopiperidino] propu) - 1H, J = 1.5 y 8.5 Hz), 7.21 indazol-5-yl] -5-fluoro- (d, 1H, J = 8.8 Hz), 7.19 (s, 2,4-pyrip? Idindiamine 1H), 6.88 (d, 1H, J = 8.8 Hz), 4.35 (t, 2H, J = 7.0 Hz 1H NMR (DMSO-d6): d (S) -N2- [l- [3- (2.6-10.78 (s, 1H), 10.49 (s, 1H), Dioxopiperidino] propyl) -10.44 (s, 1H), 8.21 (d, 1H, J indazol-5-yl] -5-fluoro- = 4.9 Hz), 7.85 (s, 1H), 7.82 61 N4- (2-methyl-3-oxo- (s, 1H), 7.56 (d, 1H, J = 8.8 + + 2H, 4H-benz [1,4] oxazin-Hz), 7.31 (d, lH, J = 8.8 Hz), 6-il) -2.4- 7.17 (s, lH), 7.16 (d, 1H, J = 8.8 Hz), 6.86 (d, 1H, J = 8.8 Hz), 4.59 (qt, 1H , J = No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 11.10 (s, 1H), 9.22 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.18 (s, 1H), 8.12 (d, 1H, J = 4H-5-? irid [l, 4] oxazin- 3.2 Hz), 8.05 (s, 1H), 7.84 (s, 6-yl) -N2- [l- [3- (2,6- 862 1H), 7.58 (d, lH, J = 8.2 Hz), + + dioxopiperidine] propyl) in 7.48 (s, 2H), 7.36 (d, 1H, J = dazol-5-yl] -5-fluoro-2,4- 8.2 Hz), 4.32 (t, 2H, J = 7.3 pyrimidinediamine Hz), 3.66 (t, 2H, J = 7.3 Hz), 2.45 (t, 2H, J = 7.3 1 H NMR (DMSO-d6): d Hydrogen chloride salt 10.33 (s, 1H), 10.23 ( s, 1H), of N4- (3.4- 8.32 (d, 1H, J = 4.7 Hz), 8.03 Dichlorophenyl) -5-fluoro- (d, 1H, J = 2.0 Hz), 7.90 (s, 863 + + N2- (2-trifluoromethyl-1H-1H), 7.74 (d, lH, J = 2.0 Hz), be nzimidazol-5-yl) -2.4-7.69 (d, 1H, J = 8.8 Hz), 7.51 pmrmdindiamine (d, 1H, J = 8.8 Hz), 7.45 (dd, lH, J = 2.0 and 8.8 Hz). 1 H NMR (DMSO-d 6): d Salt of acid 10.11 (s, 1H), 9.92 (s, 1H), ethanesulfonic acid of N4- 8.27 (d, 1H, J = 4.4 Hz), 8.06 (3,4-Dichlorophenyl) -5- (d, 1H, J = 2.0 Hz), 7.94 (s, 864 fluoro-N2- (2-1H), 7.76 (d, lH, J = 2.0 Hz), trifluoromethyl-1H- 7.67 (d, 1H , J = 8.8 Hz), 7.51 benzimidazol-5-yl) -2,4- (d, 1H, J = 8.8 Hz), 7.41 (dd, pyrimidiamine 1H, J = 2.0 and 8.8 Hz), 2.42 (qt, 2H , J = 7.3 Hz), 1 H NMR acid salt (DMSO-d6): d-benzenesulfonic acid of N4- 10.25 (s, 1H), 10.04 (s, 1H), (3,4-dichlorophenyl) -5- 8.29 ( d, 1H, J = 4.4 Hz), 8.03 65 fluoro-N2- (2- + (s, 1H), 7.91 (s, 1H), 7.73- trifluoromethyl-lH- 7.26 (m, 2H), 7.58-7.43 ( m, benzimidazol-5-yl) -2.4- 4H), 7.29-7.27 (m, 3H). pyrimidydiamyia 1 H NMR (DMSO-d 6): d P-10-30 (s, 1H), 10.08 (s, 1H), toluenesulfonic acid of N4- 8.30 (d, 1H, J = 4.7 Hz), 8.03 (3.4 -Dichlorophenyl) -5- (d, 1H, J = 2.0 Hz), 7.90 (s, 66 fluoro-N2- (2- + 1H), 7.71 (d, 2H, J = 8.8 Hz), trifluoromethyl-lH-7.51 (d, 1H, J = 8.8 Hz), benzimidazol-5-yl) -2.4-7.47-7.43 (m, 3H), 7.10 (d, pyrimidindiamine 2H, J = 8.8 Hz), 2.26 (s, 3H). lH NMR (DMSO-d6): d 9.77 (s, 1H), 9.74 (s, 1H), Salt of acid 8.25 (d, 1H, J = 3.8 Hz), 8.14 benzenesulfonic of N4- (d, 1H, J = 2.3 Hz), 8.12 (s, (3,4-Dichlorophenyl) -5- 867 lH), 7.81 (dd, 1H, J = 2.3 + fluoro-N2- (2-methyl-3H- and 8.8 Hz), 7.66 ( d, 2H, J = benzimidazol-5-yl) -2.4- 9.1 Hz), 7.59-7.52 (m, 3H), pyrimidinediamine 7.33-7.27 (m, 3H), 2.74 (s, 3H).

No. Compound Name Physical Data Triptase Triptase Triptase f_syk Com LD, ID, ID, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.78 (s, 1H), 9.74 (s, 1H), Salt of p-8.25 acid (d, 1H, J = 3.8 Hz), 8.14 N-toluenesulfonic acid (d, 1H, J = 2.3 Hz), 8.12 (s, (3,4-Dichlorophenyl) ) -5- 868 1H), 7.81 (dd, 1H, J = 2.3 and + fluoro-N2- (2-methyl-3H-8.8 Hz), 7.66 (d, 2H, J = 9.1 benzimidazol-5-yl) - 2.4- Hz), 7.54 (d, lH, J = 8.8 Hz), pyrirm ^ mdiamine 7.46 (d, 2H, J = 8.2 Hz), 7.10 (d, 2H, J = 8.2 Hz), 2.7 1H NMR ( DMSO-d6): d chloride salt of 9.93 (s, 2H), 8.28 (d, 1H, J = hydrogen of N4- (3.4-3.8 Hz), 8.12 (d, 1H, J = 2.3 Dichlorophenyl) - 5-fluoro- 869 Hz), 8.07 (s, 1H), 7.81 (dd, N2- (2-methyl-3H-1H, J = 1.8 and 8.8 Hz), 7.66 benzimidazol-5-yl) -2.4- (d, 2H, J = 8.8 Hz), 7.56 (d, pyrimidinediamine 1H, J = 8.8 Hz), 2.75 (s, 3H). 1 H NMR (DMSO-d 6): d 9.75 (s, 2H), 9.72 (s, 1H), Salt of acid 8.24 (d, 1H, J = 3.8 Hz), 8.14 ethanesulfonic of N4- (d, 1H, J = 2.0 Hz), 8.12 (s, (3,4-Dichlorophenyl) -5- 870 1H), 7.82 (d, 1H, J = 8.8 fluoro-N2- (2-metii-3H- + Hz), 7.66 (d, 2H, J = 8.5 Hz), benzimidazol-5-yl) -2.4-7.53 (d, 1H, J = 8.8 Hz), 2.74 pyrimidinediamine (s, 3H), 2.40 (qt, 2H, J = 7.3 Hz) , 1.05 (t, 3H, J = 7.3 H 1 H NMR (DMSO-d 6): d 10.37 (s, 1H), 10.23 (s, 1H), N 4 - (3-Chloro-4- 8.25 (d, 1H, J = 5.3 Hz), 7.92 methoxyphenyl) -N2- [l- (3- (s, 1H), 7.83 (s, 1H), 7.74 (d, 871 ethoxypropyl) indazole-5-1H, J = 2.6 Hz), 7.59 (d, H, J + + ü] -5-fluoro-2,4- = 8.8 Hz), 7.53 (dd, 1H, J = pyr ^ dindiamine 2.3 and 8.5 Hz), 7.38 (dd, 1H, J = 1.8 and 8.8 Hz), 7.09 (d, 1H, J = 9.1 Hz), 4.40 1 H NMR (DMSO-d6): d 10.27 (s, 1H), 10.02 (s, 1H), 8.28 (d, N4- (3, 4-Dichlorophenyl) - 1H, J = 4.7 Hz), 8.02 (d, 1H, J = N2- [l- (3- 2.3 Hz), 7.95 (s, 1H), 7.87 (s, 72-ethoxypropyl) indazole-5 - 1H), 7.68 (d, 1H, J = 8.8 Hz), il] -5-fluoro-2,4- 7.60 (d, 1H, J = 8.8 Hz), 7.51 pyrimidindiamia (d, lH, J = 8.8 Hz), 7.42 (dd, 1H, J = 2.3 and 8.8 Hz), 4.41 (t, 2H, 1H NMR (DMSO- d6): d 10.76 N4- (2,2-Dimethyl-3-oxo- (s, 1H), 10.36 (s, ÍH), 10.19 (s, 4H-benz [1,4] oxazin-6- 1H), 8.22 (d, 1H, J = 5.3 Hz), il) -N2- [l- (3- 7.90 (s, 2H), 7.55 (d, lH, J = 9.1 73 + ethoxypropyl) indazole-5 Hz), 7.37 (dd, lH, J = 1.8 and 8.8 + il] -5-fluoro-2,4-Hz), 7.20 (d, 1H, J = 8.8 Hz), pyrir dindiamine 7.18 (s, lH), 6.87 (d , lH, J = 8.8 Hz), 4.39 (t, 2H, J = 6.7 Hz No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1 H NMR (DMSO-d 6): d 10.79 (s, 1H), 10.40 (s, 1H), (S) -N2- [l- (3- 10.24 (s, 1H), 8.22 (d, 1H, J Ethoxypropyl) indazole-5- = 5.3 Hz), 7.90 (d, 1H, J = il] -5-fluoro-N4- (2-methyl-874 1.8 Hz), 7.88 (s, 1H), 7.57 + 3-oxo-2H, 4H- (d, 1H, J = 9.1 Hz), 7.37 (dd, benz [1,4] oxazin-6-yl) - 1H, J = 1.8 and 9.1 Hz), 7.22 2.4 -pyrimidindiamine (dd, 2H, J = 1.8 and 8.5 Hz), 6.89 (d, lH , J = 8.5 Hz), 4. 1H NMR (DMSO-d6): d 11.10 (s, 1H), 9.22 (s, 1H), N4- (2,2-Dimethyl-3-oxo- 9.19 (s, lH ), 8.11 (d, 1H, J = 4H-5-pyrid [1,4] oxazin- 3.5 Hz), 8.05 (s, 1H), 7.84 (s, 6-yl) -N2- [l- (3- 875 1H), 7.58 (d, lH, J = 8.5 Hz), ethoxypropyl) indazole-5- + 7.42 (d, 2H, J = 8.8 Hz), 7.35 il] -5-fluoro-2,4- (d, 1H, J = 8.5 Hz), 4.37 (t, idindiamine piri 2H, J = 6.7 Hz), 3.32 (qt, 2H, J = 7.0 Hz), 3.28 (t 1H NMR (DMSO-d6): d N4- (2 -Cloro-3- 10.32 (s, 1H), 9.63 (s, 1H), methoxypyrid-6-yl) -5- 8.19 (d, lH, J = 4.1 Hz), 8.06 876 fluoro-N2- (3,4 , 5- (d, 1H, J = 8.5 Hz), 7.52 (d, + trimethoxyphenyl) -2,4- 1H, J = 8.5 Hz), 6.91 (s, 2H), pyrimidiamine 3.88 (s, 3H), 3.64 (s, 6H), 3.61 (s, 3H). 1 H NMR (DMSO-d 6): d 9.84 (s, 1 H), 9.23 (s, 1 H), N 4 - (2-Chloro-3- 8.15 (d, 1 H, J = 8.8 Hz), 8.14 methoxypyrid-6-yl ) -N2- (d, 1H, J = 3.5 Hz), 7.55 (d, 877 (3,4-dimethoxyphenyl) -5- 1H, J = 9.1 Hz), 6.90 (d, 1H, + fluoro-2,4) - J = 2.3 Hz), 6.08 (d, 2H, J = 2.3 Hz), 3.88 (s, 3H), 3.65 (s, 3H). 1 H NMR (DMSO-d 6): d 9.83 (s, 1 H), 9.26 (s, 1 H), N 2 - (3-Chloro-4- 8.14 (d, 1 H, J = 3.5 Hz), 8.01 methoxyphenyl) -N 4- (2- (d, 1H, J = 9.1 Hz), 7.80 (d, 878 chloro-3-methoxypyrid-6- 1H, J = 2.6 Hz), 7.59 (d, 1H, il) -5-fluoro-2, 4- J = 9.1 Hz), 7.43 (dd, 1H, J = pyrimidinediamine 2.6 and 9.1 Hz), 7.03 (d, 1H, J = 9.1 Hz), 3.88 (s, 3H), 3.78 (s, 3H). lH NMR (DMSO-d6): d N4- (2-Chloro-3- 9.79 (s, 1H), 9.15 (s, 1H), methoxypyrid-6-yl) -N2- 8.13 (d, 1H, J = 3.5 Hz), 8.08 879 (3,5-dimethylphenyl) -5- (dd, lH, J = 2.3 and 8.8 Hz), + fluoro-2,4-7.57 (d, 1H, J = 8.8 Hz), 7.22 (s) , 2H), 6.53 (s, 1H), 3.82 (s, 3H), 2.19 (s, 6H). H +).

No. Name of Compound Physical Data Triptase Triptase Triptase f_syk Com LD, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 9.84 (s, 1H ), 9.32 (s, 1H), N4- (2-Chloro-3- 8.14 (d, 1H, J = 3.5 Hz), 8.12 methoxypyrid-6-yl) -5- (d, 1H, J = 8.8 Hz) , 7.96 (qt, fluoro-N2- [3- (N- 880 1H, J = 4.7 Hz), 7.60 (d, 1H, methylamin) carboml- J = 8.8 Hz), 7.37 (app s, 1H), metiiioxyphenyl] -2.4- 7.23 (d, 1H, J = 8.2 Hz), 7.13 pyrirm ^ mydiamy (t, 1H, J = 8.2 Hz), 6.48 (dd, lH, J = 2.3 and 8.2 Hz 1H NMR (DMSO-d6 ): d 2-Chloro-N 4 - (2-chloro-3-3.33 (d, 1H, J = 8.8 Hz), 8.12 881 methoxypyrid-6-yl) -5- (d, 1H, J = 2.3 Hz), 7.65 (br fluoro-4-pyrimidinamine s, 1H), 7.38 (d, 1H, J = 8.8 Hz), 3.94 (s, 3H), N4- (2-Chloro-3-CLEM: time ret .: 10.99 methoxy? irid-6-yl) -5- 882 min, purity: 93%; EM fluoro-N2- (indazol-6-yl) - + (m / e): 386 (MH). 2,4-pyrimidinediamine N4- (2-Chloro-3-methoxy-irid-6-yl) -5-LCMS: retentate time: 11.74 fluoro-N2- (2-883 min., Purity: 97%; ü- 1 H- (m / e): 454 (MH1). benzimidazol-5-yl) -2,4-pyrin? dmcüaniina N4- (2-Chloro-3-methoxypyrid-6-yl) -5- CLEM: ret. time: 7.71 884 fluoro-N2- (2-methyl-3H - min, purity: 93%, EM benzimidazol-5-yl) -2,4- (m / e): 400 (MH *). pMn? dmdiamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-CLEM: retin time: 12.20 885 fluoro-N2- (lmin; purity: 93%; EM + methylindazole-6-) il) -2.4- (m / e): 400 (MH4). pyrimidinediamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-CLEM: time ret .: 10.79 886 fluoro-N2- (l-min, purity: 94%, methyl methylin-5-yl) - 2.4- (m / e): 400 (MH4). pyrimid diamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-CLEM: retentate time: 12.97 87 fluoro-N2- (l-min, purity: 95%, EM + ethylindazol-6-yl ) -2.4- (m / e): 414 (MH4). pyrimidinediamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-CLEM: time ret .: 13.86 fluoro-N2- (l-min, purity: 92%, EM + isopropylindazole-6-y) - (m / e): 428 (MH4). 2,4-? Irimidindiamine No. Name of Compound Physical Data Tftase Triptase Tftasa f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (2-Chloro-3- methoxypyrid-6-yl) -N2-CLEM: ret time: 11.84 (2,2-dimethyl-3-oxo-4H-889 min., purity: 94%; EM benz [1,4] oxazin-6-yl ) -5- (m / e): 445 (MH). fluoro-2,4-pipipid diamine N 2 - [l- [3- (N-Acetylamino) propyl] inda CLEM: ret. time: 9.42 zol-5-ü] -N4- (2-chloro-3-890 min, purity: 95%, MS + methoxy? irid-6-yl) -5- (m / e): 485 (MH4 ). fluoro-2,4-pyriridinediamine N 4 - (2-Chloro-3-methoxypyrid-6-yl) -N 2 - [l- [3- (N-CLEM: time retained: 10.30 891 cyclopropanecarbonylmin, purity: 95 %; MS + amino) pro? Il] indazol-5 (m / e): 511 (MH4). il] -5-fluoro-2,4-pyrimidindiamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-LCMS: time ret .: 11.73 fluoro-N2- [1- (3-892 min. purity: 99%; EM + pivalamidopropyl) - (m / e): 527 (MH4). indazol-5-yl] -2,4-pyrirm ^ indiamine N4- (2-Chloro-3-methoxypyrid-6-yl) -5-CLEM: time ret .: 10.71 fluoro-N2- [l- [3- ( N- 893 min, purity: 97%, ME + isobutyrylamino) propi] - (m / e): 514 (MH4). indazol-5-yl] -2,4- p -idiidindiamine N 4 - (3,4-Dichlorophenyl) -N 2 - (1, 2-LCMS: ret. time: 9,44,894 dimethylbenzimidazole-5 min., purity: 100%; MS + ñ) -5-fluoro-2,4- (m / e): 418 (MH4). pyrimid diamine N 4 - (3-Chloro-4-methoxyphenyl) -N 2 - (1, 2-LCMS: retentate time: 7.66 895 dimethylbenzimidazole-5 min, purity: 96%, EM + il) -5-fluoro- 2.4- (m / e): 413 (MH4). pyrimidinediamine N2- (1, 2-dimethylbenzimidazol-5-yl) -N4- (2,2-dimethyl-3-CLEM: time ret .: 7.09 896 oxo-4H-min, purity: 99%, EM + benz [ 1,4] oxazin-6-yl) -5- (m / e): 448 (MH4). fluoro-2,4-pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt (S) -N2- (1 2- Dimethylbenzimidazole-5 LCMS: Ret time: 6.52 il) -5-fluoro-N4- (2-ethyl- 897 min, purity: 97%, EM + + 3-oxo-2H, 4H- + ( m / e): 434 (MH4) .benz [1,4] oxazin-6-yl) -2,4-pyrimidinediamine N2- (1, 2-dimethylbenzimidazol-5-yl) -N4- (2,2-dimethyl) -3- LCMS: time ret .: 7.85 898 oxo-4H-5 min., Purity: 91%; MS + + pyridfl, 4] oxazin-6-yl) -5- (m / e): 449 (MH4 ). Fluoro-2,4-pyrimidine diamine N 4 - (3,4-Dichlorophenyl) -5-fluoro-N 2 - [1- (2-CLEM: ret time: 8.77 899 hydroxyethyl) -2- min.; purity: 97%; MS + methylbenzimidazol-5-yl) - (m / e): 448 (MH4). 2,4-pyrimidinediamine N 4 - (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret time: 7.06 900 N 2 - [1- (2-hydroxyethyl) -2- min; purity: 93%; MS + methylbenzimidazol-5-yl) - (m / e): 443 (MH4). 2,4-pyrimidindiamine N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-CLEM: ret. Time: 6.50 il) -5-fluoro-N2- [l- ( 2- 901 min, purity: 97%, hydroxyethyl EM) -2- (m / e): 478 (MH4). Methylbenzimidazol-5-yl) -2,4-pyrimidinediamine (S) -5-Fluoro-N2- [l- (2-hydroxyethyl) -2-methylbenzimidazol-5-yl) - CLEM: ret time: 5.99 902 N4- ( 2-methyl-3-oxomin, purity: 94%; MS + + 2H, 4H-benz [1,4] oxazin- (m / e): 464 (MH4) .6-yl) -2.4 - pyrirm ^ indiamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-CLEM: time ret .: 6.89 6-ü) -5-fluoro-N2- [l- (2- 903 min, purity: 97%; EM + hydroxyethyl) -2- + (m / e): 479 (MH4). methylbenzimidazol-5-yl) -2,4-? irimidindiamine N4- (3,4-Dichlorophenyl) -N2- (2,3-dihydro-l-methyl-CLEM: ret. time: 10.32 904 2-oxo-benzimidazole- 5- min., Purity: 100%; EM ü) -5-fluoro-2,4- (m / e): 420 (MH4). pyrimidimdiamine No. Name of Compound Physical Data Triptase Triptase Triptase f_syk Com ID, ID, ID, Cpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (3-Chloro-4-methoxyphenyl) -N2- ( 2.3 LCMS: time ret .: 8.24 905 dihydro-l-methyl-2-oxomin, purity: 96%, EM + benzimidazol-5-yl) -5- (m / e): 415 (MH4 ). fluoro-2,4-pyrimidinediamine N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-yl) -N2- (2,3-dihydro-l-CLEM: time ret : 7.53 906 methyl-2-oxomin, purity: 97%; MS + + benzimidazol-5-yl) -5- (m / e): 450 (MH4). fluoro-2,4-pyrimidiamine (S) -N2- (2,3-Dihydro-1-methyl-2-oxo-907) 908 909 + eleven 12 pir midindiamine No. Compound Name Physical Data Triptase Tftasa Tftasa f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T N4- (2,2-Dimethyl-3 -oxo-4H-benz [1,4] oxazin-6-LCMS: ret time: 10.21 il) -N2- (1-methyl-2-913 min, purity: 94%, trifluoromethyl-EM + (m / e): 502 (MH4), benzimidazol-5-yl) -2,4-p-methylindiamine (S) -5-Fluoro-N4- (2-methyl-3-oxo-2H, 4H-benz [1,4] oxazin -6-yl) -MSC: time ret .: 9.66 914 N2- (1-methyl-2 min., Purity: 93%; EM + trifluoromethyl- (m / e): 488 (MH) .benzimidazole-5 il) -2,4- pyrinidinediamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-CLEM: retentate time: 11.48 6-yl) -N2- (l- methyl-2- 915 min., purity: 91%; trifluoromethyl- + EM (m / e): 503 (MH4), benzimidazol-5-yl) -2,4-pyrirm ^ indiamine N4- (3,4-Dichlorophenyl) ) -5- fluoro- [1- (2-hydroxyethyl) -MSCM: time ret: 12.15 916 2-trifluoromethylmin; purity: 96%; MS + benzimidazol-5-yl] -2,4- (m e): 502 (MH4). pijrirnidindiamine N 4 - (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret time: 9.90 [l- (2-hydroxyethyl) -2- 917 min; purity: 94%; Trifluoromethyl- + (m / e): 497 (MH4). benzimidazol-5-yl] -2,4-pyrimidinediamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-yl) -5-fluoro- [1- (2- LCMS: ret. Time: 9.08-18 hydroxyethyl) -2- min; purity: 96%; MS + trifluoromethyl- (m / e): 532 (MH4). benzimidazol-5-ñ] -2,4-pyrirmdmdiamine (S) -5-FTuoro- [l- (2-hydroxyethyl) -2-trifluoromethyl-CLEM: ret. time: 8.67 19 benzimidazol-5-yl] -N4- min .; purity: 92%; MS + + (2-methyl-3-oxo-2H, 4H- (m / e): 518 (MH4). Benz [1,4] oxazin-6-yl) -2,4-pyridinidinediamine N4- ( 3,4-Dichlorophenyl) -5-fluoro- [l- (2-hydroxymethyl) -2-LCMS: ret time: 14.96 20 min; purity: 97%; Trifiuoromethyl- (m / e): 486 (MH). benzimidazol-5-yl] -2,4- pyrimidinediamine No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- ( 3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret. Time: 12.21 [1- (2-hydroxymethyl) -2-921 min; purity: 98%; MS + + trifluoromethyl- (m / e): 481 (MH4). benzimidazol-5-yl] -2,4-pyrimidindiainine N 4 - (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-yl) -5-fluoro- [1- (2- LCMS: ret time: 10.93 922 hydroxymethyl) -2- min; purity: 96%; Trifluoromethyl- (m / e): 516 (MH4). benzimidazol-5-yl] -2,4- pijrir dmdiamine (S) -5-Fluoro- [l- (2-hydroxymethyl) -2- trifluoromethyl-CLEM: ret time: 10.43 923 benzimidazol-5-yl] -N4- min .; purity: 92%; MS + (2-methyl-3-oxo-2H, 4H- (m / e): 502 (MH4). Benz [1,4] oxazin-6-yl) -2,4-pyrimidine diamine N4- (2.2 -Dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro- [1- (2-CLEM: ret. Time: 12.25 924 hydroxymethyl) -2- min; purity: 98%; MS + trifluoromethyl- (m / e): 517 (MH4). benzimidazol-5-yl] -2,4- pyriniidindiamine N2- (1,2-Benzisoxazole-CLEM: time ret .: 9.63 5-yl) -N4- (3-chloro-4-925 min, purity: 100%; MS methoxypheni) -5-fluoro- (m / e): 386 (MH4). 2,4-? Irimid diamine N2- (1, 2-Benzisoxazol-5-yl) -N4- (2,2-dimethyl-3-CLEM: ret time: 8.48 oxo-4H-926 min., Purity: 100%; MS + benz [1,4] oxazin-6-yl) -5- (m / e): 421 (MH). fluoro-2,4-pyrimidinediamine (S) -N2- (1, 2-Benzisoxazol-5-yl) -5-CLEM: time ret .: 8.11 fluoro-N4- (2-methyl-3-27 min.) purity : 100%; oxo-2H EM, 4H- (me): 407 (MH4), benz [1,4] oxazin-6-yl) -2,4-pyrimaminamine N2- (1,2-Benzisoxazole) -u) -N4- (2,2-dimethyl-3-LCMS: ret time: 9.57 oxo-4H-5-min, purity: 100%, pyrido-EM [1,4] oxazin-6-yl) - (m / e): 422 (MH4). 5-Fluoro-2,4-pyrimidiadia ina No. Compound Name Physical Data Triptase Tftase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IE, 8pt Ion, 3pt racemic-N2- ( 1, 2-Benzisoxazol-5-yl) -5- LCMS: time ret .: 9.69 fluoro- (2-methyl- 1,1,3-929 min, purity: 95%, trioxo-2H, 4H- EM ( me): 455 (MH4) benzo [1,4] thiazin-6-yl) -2,4-pijrir dindiamine N2- (1,2-benzisoxazol-5-yl) -N4- (2,2-dimethyl- LCMS: ret time: 10.13 L, 1, 3-trioxo-4H-930 min, purity: 97%, MS + benzo [1,4] thiazin-6-yl) -5- (m / e): 470 (MH4). racemic fluoro-2,4-p? imidmdiamine-N2- (1, 2-Benzisoxazol-5-yl) -5-CLEM: ret time: 9.21 fluoro-N4- (2-methyl-3-931 min.; purity: 96%; Ox oxo-2H, 4H- (m / e): 423 (MH4). benz [1,4] thiazin-6-yl) -2,4-pyrimidmdiaminz N 4 - (3,4-dichlorophenyl) - N 2 - (l-ethyl-2-CLEM: ret time: 10.09 932 methylbenzimidazol-5-yl) - min .; purity: 99%; 5-Fluoro-2,4- MS (m / e): 432 (MH4). pyrimidindiaminz N4- (3-Chloro-4-methoxyphenyl) -N2- (l-ethyl-CLEM: ret time: 8.64 933 2-methylbenzimidazole-5 min., purity: 92%; EM + ñ) -5-fluoro- 2.4- (m / e): 427 (MH4). pyrimidindiamine N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxacin-6-LCMS: ret. time: 7.91 ü) -N2- (1- et-2- 934 min. 99%; EM methylbenzimidazol-5-yl) - (m / e): 462 (MH4). 5-fluoro-2,4-pyrimidiamine (S) -N2- (1-Ethyl-2-methylbenzimidazol-5-yl) -MSCM: time ret: 7.72 5-fluoro-N4- (2-methyl-3-35 min. purity: 95%; oxo-2H EM, 4H- (m / e): 448 (MH4), benz [1,4] oxacin-6-yl) -2,4-pyriimidine N4- (2,2- Dimethyl-3-oxo-4H-5-pyrido [1,4] oxacin-CLEM: Ret. Time: 8.48 6-ü) -N2- (1- ethyl-2- 36 min., Purity: 96%; methylbenzimidazole EM -5-il) - (m / e): 463 (MH4). 5-Fluoro-2,4-pyrimidmdiamine No. Name of Compound Physical Data Tftase Triptase Triptase f syk Com LD, LD, ID, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (3,4 -Dichlorophenyl) -5- fluoro-N2- [l- (3-CLEM: ret. Time: 12.33 hydroxypropyl) -2- 937 min; purity: 97%; MS + + trifluoromethyl-benzimidazol-5-yl] -2,4- (m / e): 516 (MH4). pyrimidinediamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret .: 9.85 N2- [1- (3-hydroxypropyl) -938 min; purity: 94%; EM + 2-trifluoromethyl-benzimidazol-5-yl] -2,4- (m / e): 511 (MH4). pyr ^ dindiamine N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-yl) -5-fluoro-N2- [l- (3-CLEM: ret. time: 9.04 939 hydroxypropyl) -2- min; purity: 96%; MS + + trifluoromethyl- (m e): 546 (MH4). benzimidazol-5-yl] -2,4-pyrianedi-diamine (S) -5-Fluoro-N2- [l- (3-hydroxypropyl) -2- trifluoromethyl-CLEM: ret time: 8.49 940 benzimidazol-5-yl] -N4 - min .; purity: 95%; EM + + (2-methyl-3-oxo-2H, 4H- (m / e): 532 (MH4). Benz [1,4] oxazin-6-yl) -2,4-? Irimidindiamine N4- (2 , 2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-6-yl) -5-fluoro-N2- [l- (3-CLEM: ret. Time: 9.85 941 hydroxypropyl) -2 - min .; purity: 93%; MS + + trifluoromethyl- (m / e): 547 (MH4). benzimidazol-5-yl] -2,4-pyrirmdmdiamine N4- (3,4-Dichlorophenyl) -5- fluoro-N2- [l-methyl-2- (4- CLEM: ret. time: 9.49 42 min., purity : 97%; MS + + (m / e): 489 (MH4). N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-N2- [l-methyl-2- (4- CLEM: time ret .: 7.79 43 min., Purity: 93%; EM morpholin) benzimidazole- + (m / e): 484 (MH4) .5-ü] -2,4- pyrimidindiamine N4- (2,2-Dimethyl-3- oxo-4H-benz [1,4] oxazin-6-LCMS: ret time: 7.20 ñ) -5-fluoro-N2- [1-methyl-44 min, purity: 99%; MS + 2- (4- morpholin) - (m / e): 519 (MH4), benzimidazol-5-yl] -2,4-pyrimidinediamine or Compound Name Physical Data Triptase Triptase Tftase f_syk om LD, ID, ID, llpt CMC, CMC, CMC , IgE, 3pt IgE, 8pt Ion, 3pt (S) -5-Fluoro-N2- [l-methyl-2- (4-morpholino) benzimidazole-CLEM: ret time: 6.78 945 5-yl] -N4- (2-methyl-3-oxo-ruin; purity: 90%; EM + 2H, 4H-benz [1,4] oxazin- (m / e): 505 (MH4). pyridi-dindiamine N4- (2,2-Dimethyl-3-oxo- 4H-5- pyrido [1,4] oxazin-6-yl) -5-fluoro-N2- [1-CLEM: ret time: 7.86 946 methyl-2- (4 min, purity: 96%, EM + + morpholine) benzimidazole - (m / e): 520 (MH4). 5-yl] -2,4-pyrimidindiamine N 4 - (3,4-Dichlorophenyl) -5- fluoro-N 2 - [l- (3-CLEM: time ret .: 9.65 947 hydroxypropyl) -2- min, purity: 95%, EM + methylbenzimidazol-5-yl] - (m / e): 462 (MH4) 2,4-pyrimid diamide N4- (3-Chloro-4- methoxyphenyl) -5-fluoro-CLEM: ret. time: 8.28 948 N2- [1- (3-hydroxypropyl) -min, purity: 90%, EM + 2-methylbenzimidazole-5 (m / e): 457 ( MH4) N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-CLEM: ret. Time: 7.70 il) -5-fluoro- N2- [1- (3- 949 min., Purity: 96%; hydroxypropyl EM) -2- + (me): 492 (MH4), methylbenzimidazol-5-yl] -2,4-? -i? Midindiamine (S) -5-Fluoro-N2- [l- (3- hydroxy? ropil) -2- methyl benzimidazol-5-yl] -MSCM: time ret .: 7.22 950 N4- (2-methyl-3-oxo-min; purity: 90%; MS 2 H, 4 H -benz [1,4] oxazin- (m / e): 478 (MH4). 6-ü) -2,4- pyrimid diamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-CLEM: ret time: 7.97 6-ü) -5-fluoro - N2- [1- (3-951 min, purity: 94%, hydroxypropyl EM) -2- + + (m / e): 493 (MH4). methylbenzimidazol-5-yl] -2,4-pyrimidinediamine N2- [l- [3 - (/ V-Acetylamino) propyl] -2- methylbenzimidazol-5-yl] - CLEM: time ret: 7.89 52 N4- ( 2,2-dimethyl-3-oxomin, purity: 97%; MS + + 4H-benz [1,4] oxazin-6- (m / e): 533 (MH4). Ü) -5-fluoro -2,4- pirpmdindiamine No. Compound Name Physical Data Triptase Tftase Triptase f_syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- [l- [3- (iV - Acetylamino)? Ro? Il] -2- methylbenzimidazol-5-yl] - CLEM: ret time: 8.09 953 N4- (2,2-Dimethyl-3-oxo- mine, purity: 97%, EM + 4H- 5-pyrido [1,4] oxazin- (me): 534 (MH4) .6-yl) -5-fluoro-2,4-pyrimimidhamine N4- (3,4-dichlorophenyl) -5-fluoro-N2 - [1-methyl-2- (4-CLEM: ret time: 10.04 954 morpholinyl) -min; purity: 96%; MS + benzimidazol-5-yl] -2.4- (m / e): 503 (MH4). pyrimidindiainine N 4 - (3-Chloro-4-methoxyphenyl) -5-fluoro-N 2 - [l-methyl-2- (4-CLEM: ret time: 9.29 955 min, purity: 93%, morpholinylmethyl) -benzimidazole- 5-yl] -2.4- (m / e): 498 (MH4). pyrirnidinediamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-CMS: time ret .: 8.09 il) -5-fluoro-N 2 - [1-methyl-956 min.; purity: 94%; MS 2- (4-morpholinylmethyl) - (m / e): 533 (MH4). benzimidazol-5-yl] -2,4-p-indidinediamine (S) -5-Fluoro-N2- [l-methyl-2- (4-morpholinylmethyl) -MSCM: time ret .: 7.55 957 benzimidazol-5-yl] - N4- min .; purity: 98%; EM + + (2-methyl-3-oxo-2H, 4H- (m / e): 519 (MH4). Benz [1,4] oxazin-6-yl) -2,4-pyrimidinediamine N4- (2, 2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-6-yl) -5-fluoro-N2- [1-CLEM: ret time: 8.34 958 methyl-2- (4 min. purity: 98%; MS + morpholinemethyl) - (m / e): 534 (MH4). benzimidazol-5-yl] -2,4-pyrimid diamine N 4 - (3,4-Dichlorophenyl) -5-fluoro-N 2 - [2- (4-CLEM: time ret: 9.12 959 morpholin-methyl) -1H-min; purity: 95%; MS benzimidazol-5-yl] -2.4- (m / e): 489 (MU4). pijrirmdindiamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret time: 8.10 N2- [2- (4-60 min, purity: 97%, morpholinyl EM) - 1H- + (m / e): 484 (MH4). benzimidazol-5-yl] -2,4- pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- ( 2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-CLEM: ret time: 7.70 il) -5-fluoro-N2- [2- (4-961 min, purity: 93%; MS morpholinyl) -lH- + + (m / e): 519 (MH4). benzimidazol-5-yl] -2,4-pyrimidinediamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-CLEM: ret. time: 7.93 6-il) -5 -fluoro-N2- [2- (4-962 min, purity: 95%, morpholinylmethyl) -lH- + + (m / e): 520 (MU4). benzimidazol-5-yl] -2,4-pyrimidindiamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-yl) -5-fluoro-N 2 - [2-methyl] LCMS: time ret: 8.01 963 l- [3- (N-min, purity: 95%, MS + methylsulfonylamino) - (me): 569 (MH4). ? ro? il] benzimidazole-5- ü] -2,4-pyrj ™ dmdiamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-6-yl) -5 -fluoro-N2- [2- CLEM: time ret: 8.36 964 methyl-l- [3- (N- min.; purity: 95%; MS + + methylsulfonylamino) - (m / e): 570 (MH4). ? ropil] benzimidazol-5-yl) -2,4-pyririmidodiamine N 4 - (3,4-dichlorophenyl) -5-fluoro-N 2 -. { 1 -methyl-2-LCMS: time ret .: 10.63 965 [(methylsulfonyl) methyl] -Roman; purity: 94%; EM + benzimidazol-5-yl} -2.4- (m / e): 496 (MH4). pyrirmdmdiamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret .: 9.10 N2-. { l-metü-2- 66 min; purity: 95%; MS [(methylsulfomethyl) methyl] - + (m / e): 491 (MH4). benzimidazol-5-yl} -2,4- pyrimidindiamine N 4 - (2,2-Dimethyl-3-oxo-4 H -benz [1,4] oxazin-6-y) - CLEM: Ret. Time: 9.22 5-fluoro-N 2 -. { L-methyl-2-67 min; purity: 91%; MS + [(metilsxxlfoml) methyl] - (m / e): 525 (MH4). benzimidazol-5-yl} -2,4- pyrirmdmdiamine (S) -5-Fluoro-N2-. { 1-methyl-2 - [(methylalkonyl) methyl] -benzimidazol-5-yl} -N4- (2 LCMS: Ret Time: 8.62 68 min., Purity: 91%; Methyl-3-Oxo-2H, 4H- EM (m / e): 512 (MH4) .benz [l, 4] oxazin-6-yl) -2,4- pyrimduidiamine No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? t N4 - (2,2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-6-yl) -5-fluoro-N2-. { LCMS: time ret .: 9.14 969 methyl-2 min .; purity: 94%; MS + [(methylsulfonyl) methyl] - (m e): 527 (MH4). benzimidazol-5-yl} -2,4- pyrimidine diamine N4- (3,4-Dichlorophenyl) -MSCM: ret time: 9.42 diethyaminomethyl) -1,970 methylbenzimidazol-5-yl] -min; purity: 91%; MS + (m / e): 489 (MH4). 5-fluoro-2,4-pyrimidine diamine N4- (3-Chloro-4-methoxyphenyl) -N2- [2-CLEM: time ret: 7.76 (/ -diethylaminomethyl) -971 min; purity: 94%; MS 1 -methylbenzimidazole-5- (m / e): 485 (MH *). il] -5-fluoro-2,4- 7.56 972 EM + 7. 21 973 EM N2- [2 - (/ V ^ V- Diethylaminomethyl) -1-methylbenzimidazol-5-yl] -MSCM: Ret. Time: 7.51 974 N4- (2,2-dimethyl-3-oxo-min., Purity: 97 %; MS + + 4H-5-pyrido [1,4] oxazin- (m / e): 520 (MH4) .6-yl) -5-fluoro-2,4-pyrimidiamine N4- (3,4-Dichlorophenyl) ) -5- fluoro-N2- [2- (4- CLEM: time ret: 8.89 75 morpholin) -lH- min; purity: 90%; MS + benzimidazole-5-ü] -2.4- (m / e): 475 (MH4). pijrirm ^ mydiamine No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (2,2-Dimethyl-3-oxo - 4H-benz [1,4] oxazin-6-yl) -5-fluoro-N2- [2- (4- CLEM: ret time: 7.76 976 min, ret time: 96%, morpholin MS) -lH- (m / e): 505 (MH4). benzimidazol-5-yl] -2,4-pyrir ^ indiamine N4- (2,2-Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-CLEM: ret time: 8.05 6-ü) - 5-fluoro-N2- [2- (4-977 min, ret time: 926%; MS morpholin) -lH- (m / e): 506 (MH4). benzimidazol-5-yl] -2,4- pMmidindiamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret. time: 8.03 978 N2- [2- (4-morpholin) -lH- min; Ret time: 92%; MS benzimidazol-5-yl] -2.4- (m / e): 470 (MH4). pyrimidmdiamine N4- (3,4-Dichlorophenyl) -5- fluoro-N2- [l-methyl-2- (4-CLEM: ret. time: 8.12 979 methyl-l-? iperazin) -lH- min; Ret time: 98%; MS benzimidazol-5-yl] -2,4- (m e): 502 (MH4). pyrimidindiamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-N2- [l-methyl-2- (4-methyl-CLEM: time ret: 7.34 980 wreck; time ret .: 96%; -piperazin) -lH- (m / e): 497 (MH4). benzimidazol-5-yl] -2,4- pyrimidinediamine N4- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-CLEM: ret time: 6.99 ü) -5-fluoro- N 2 - [1-methyl-981 2- (4-methyl-1-γ-yzinzin) -min; Ret time: 97%; MS (m / e): 532 (MH4). lH-benzimidazol-5-yl] -2,4-pyrimidinediamine (S) -5-Fluoro-N2- [l-methyl-2- (4-methyl-l-piperazin) -lH-CLEM: ret. time: 6.62 82-benzimidazol-5-yl] -N4- min; Ret. time: 97%; MS (2-methyl-3-oxo-2H, 4H- (m / e): 518 (MH4). Benz [1,4] oxazin-6-yl) -2,4-pyrimidinediamine N4- (2,2- Dimethyl-3-oxo-4H-5-pyrido [1,4] oxazin-6-yl) -5-fluoro-N2- [l-CLEM: time ret .: 7.05 83 methyl-2- (4-methyl-1) min, purity: 96%, piperazine MS) -lH- (m / e): 533 (MH4). benzimidazol-5-yl] -2,4- pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt T NMR ( DMSO-d6): d Salt of acid 11.22 (1H, s), 9.79 (1H, s), benzenesulfonic of N4-9.62 (1H, s), 8.27 (1H, d, J = (2,2-Dimethyl-3 -oxo-4H- 3.9 Hz), 8.08 (1H, d, J = 4.5 5-pyrid [1,4] oxazin-6-yl) - 984 Hz), 7.68-7.64 (3H, m), 7.47 5-fluoro -N2- [3- (N- + + (1H, d, J = 8.7 Hz), 7.42-methyamin) carbonyl- 7.31 (5H, m), 7.22 (lH, t, J = methylenexyphenyl) -2.4- 8.1 Hz), 6.63 (lH, dd, J = 8.1 pijrimidindiamine Hz, J = 2.4 Hz), 4.47 (2H, T NMR (DMSO-d6): d Salt of the acid p- 11.23 (1H, s), 9.91 (1H , s), toluenesulfonic of N4- 9.70 (1H, s), 8.29 (1H, d, J = (2,2-Dimethyl-3-oxo-4H-3.9 Hz), 8.06 (1H, m), 7.65- 5 -? irid [1, 4] oxazin-6-ü) - 985 7.61 (1H, m), 7.55 (1H, d, J 5-fluoro-N2- [3- (N- + + = 8.1 Hz), 7.48 (1H, d, J = methyamin) carbonyl- 8.1 Hz), 7.33-7.18 (5H, m), methylenexyphenyl] -2.4-6.66 (lH, d, J = 7.5 Hz), 4.48 pyripindinediamine (2H, s), 2.75 (3H, d, J = 3.6! H NMR (DMSO-d6): d Hydrogen chloride salt 11.18 (1H, s), 9.54 (2H, of N4- (2 , 2-Dimethyl-3- broad s), 8.26 (1H, s), 8.05 oxo-4H-5- (1H, broad s), 7.70-7.66 pyrid [1,4] oxazin-6-yl) -5- (lH, m), 7.47 (lH, d, J = 8.4 986 fluoro-N2- [3- (N-Hz), 7.40 (1H, s), 7.34 (1H, + methylamino) carbonyl-d, J = 9 Hz), 7.20 (1H, t, J = methylenexyphenyl) -2.4- 7.9 Hz), 6.61 (1H, d, J = 7.5 pyrimidinediamine Hz), 4.47 (2H, s), 2.75 (3H, d, J T NMR (DMSO-d6): d Hydrogen chloride salt 11.18 (1H, s), 9.50 (2H, Bis of N4- (2,2-dimethyl-s), 8.25 (1H, d, J = 3-oxo-4H -5- 3.3 Hz), 8.06 (1H, m), 7.74- pyrid [1,4] oxazin-6-yl) -5- 7.67 (1H, m), 7.47 (1H, d, J 987 fluoro-N2- [3- (N- = 8.4 Hz), 7.41 (1H, s), 7.37 + methyamin) carbonyl- (1H, d, J = 8.1 Hz), 7.20 (1H, methyleneoxyphenyl) -2,4- t, J = 7.9 Hz), 6.59 (1H, d, J piimididinediamine = 8.1 Hz), 4.47 (2H, s), 2.74 (? NMR (DMSO-d6): d Nitric acid salt of 11.19 (1H, s), 9.58 (1H, N4- (2,2-Dimethyl-3-oxo-broad) ), 9.52 (1H, s), 8.25 4H-5-pyrid [1,4] ox- (lH, d, J = 3.6 Hz), 8.06 (1H, 988 6-yl) -5-fluoro-N2- [ 3- (N-m), 7.70-7.66 (1H, m), 7.47 + + methyamin) carbonyl- (lH, d, J = 8.7 Hz), 7.40 (1H, methyleneoxyphenyl) -2.4-s), 7.34 (1H, d, J = 8.1 Hz), pñinn ^ indiamina 7.21 (lH, t, J = 8.1 Hz), 6.61 (1H, d, J = 7.5 Hz), 4.47 (No. Name of Compound Physical Data Triptase Tftase Triptase F_syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d Nitric acid salt Bis 11.21 (1H, s), 9.64 (1H, de N4- (2,2-Dimethyl-3- broad s), 9.54 (1H, s), 8.26 oxo-4H-5-pyrid [1,4] ox-6-yl) -5- (lH, d, J = 3.6 Hz), 8.07 (1H, 989 m), 7.67 (1H, d, J = 8.4 Hz), + + fluoro-N2- [3- (N-methylamino) carborjyl- 7.47 (lH, d, J = 8.7 Hz), 7.39 (1H, s), 7.34 (1H, d, J = 7.8 methyleneoxyphenyl) -2.4-Hz), 7.21 (lH, t, J = 8.2 Hz), pyrimid diarynine 6.62 (lH, d, J = 8.4H z), 4 T NMR (DMSO-d6): d Salt of acid 11.24 (1H, s), 9.79 (1H, methane sulfonic of N4- broad s), 9.63 (1H, s), 8.27 (2,2-dimethyl- 3-oxo-4H- (1H, d, J = 3.9 Hz), 8.07 (1H, 5-pyrid [1,4] ox-6-yl) -990), 7.64 (1H, d, J = 8.4 Hz) , + 5-fluoro-N2- [3- (N- 7.48 (lH, d, J = 8.4 Hz), 7.36 methyamin) carbonyl- (1H, s), 7.32 (1H, d, J = 7.5 methyleneoxyphenyl) -2 , 4- Hz), 7.22 (lH, t, J = 7.9 Hz), pirin? Imdiamine 6.64 (lH, d, J = 8.7 Hz), XH NMR (DMSO-d6): d Salt of the acid (lS) - ( +) - 11.25 (1H, s), 9.72 (lH, camphorsulfonic brad of N4- s), 9.59 (1H, s), 8.27 (1H, d, (2,2-Dimethyl-3-oxo-4H- J = 3.6 Hz), 8.07 (1H, m), 5-pyrid [1,4] ox-6-yl) -991 7.65 (lH, d, J = 8.4 Hz), 7.47 + 5-fluoro-N2- [3- (N-methylamino) carbonyl- (lH, d, J = 8.7 Hz), 7.37 (1H, s), 7.33 (1H, d, J = 8.7 Hz), methylenexyphenyl] -2.4-7.21 (lH, t, J = 8.1Hz), 6.62 pirintidindiamine (lH, dd, J = 8.1Hz, J Tí NMR (DMSO-d6): d Salt of the acid (+) - 11.21 (1H, s), 9.63 (1H, camphorsulfonic of N4- broad s), 9.54 (1H, s), 8.26 (2,2-Dimethyl-3 -oxo-4H- (1H, d, J = 3.6 Hz), 8.07 (1H, 5-pyrid [1,4] ox-6-yl) - 992 m), 7.67 (1H, d, J = 8.4 Hz) , 5-fluoro-N2- [3- (N-methyamin) carbonyl- 7.47 (lH, d, J = 8.7 Hz), 7.39 (1H, s), 7.34 (lH, d, J = 8.1 methyleneoxyphenyl) -2, 4- Hz), 7.21 (lH, t, J = 8.1Hz), idindiamine piri 6.61 (1H, dd, J = 8.1Hz, J XH NMR (DMSO-d6): d 10.78 (1H, s), 10.11 (1H , Salt of p-broad acid s), 9.89 (1H, broad toluenesulfonic of N4-s), 8.29 (1H, d, J = 4.8 Hz), (2,2-Dimethyl-3-oxo-4H-8.01 (1H , s), 7.95 (1H, s), 93 benz [l, 4] ox-6-yl) -5- + + 7.70 (lH, d, J = 8.7 Hz), 7.55 fluoro-N2- (l- ( 2H, d, J = 8.1Hz), 7.40 (1H, methylindazol-6-yl) -2,4-d, J = 8.4 Hz), 7.29-7.18 pyrimidinadiarmin (4H,), 6.95 (1H, d, J = 8.7 Hz), No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T lH NMR (DMSO-d6) : d Salt of the acid p-10.73 (1H, s), 9.65 (1H, s), toluenesulfonic of N2-9.41 (1H, s), 8.20 (lH, d, J = (3-Chloro-4-methoxy-5) - 4.2 Hz), 7.7 1 (1H, s), 7.54 methyphenyl) -N4- (2,2-994 (2H, d, J = 8.1 Hz), 7.43 (1H, dimethyl-3-oxo-4H- + + + s), 7.35 (lH, dd, J = 8.4 Hz, J benz [1,4] ox-6-yl) -5- = 2.4 Hz), 7.23-7.17 (3H, m), fluoro-2,4-7.00 (lH, d, J = 8.4 Hz), 3.76 piriinidmdiamma (3H, s), 2.38 (3H, s) * H NMR (DMSO-d6): d 9.19 (1H, d, J = 1.5 Hz), 9.05 N2- (3- Chloro-4-hydroxy- (1H, s), 8.64 (1H, s), 8.10 5-methylphenyl) -N4- (3,4- (1H, d, J = 3.9 Hz), 7.62 (1H, 995 ethylenedioxyphenyl) -5- d, J = 2.7 Hz), 7.36 (lH, d, J = + fluoro-2,4- 1.8 Hz), 7.31 (1H, m), 7.27 pyrimidine diamine (1H, d, J = 2.7 Hz) , 6.87 (1H, d, J = 8.4 Hz), 4.31 (4H, s), 2.22 (3H, s); LCMS: purity: T NMR (DMSO-d6): d 11.16 (1H, s), 9.27 (1H, s), N2- (3-Chloro-4-hydroxy-9.15 (1H, s), 8.67 (1H, s) ), 5-methylfeml) -N4- (2.2- 8.19 (1H, d, J = 3.6 Hz), 7.64 dimethyl-3-oxo-4H-5-996 (2H, m), 7.42 (1H, d, J = 8.4? Irid [1,4] oxazin-6-yl) -5- + Hz), 7.29 (1H, d, J = 2.7 Hz), fluoro-2,4-2.22 (3H, s), 1.53 ( 6H, s); pyrimidinediamine LCMS: purity: 97.69%; MS (m / e): 444 (M +). XH NMR (DEMO-d6): d 11.16 (1H, s), 9.23 (1H, s), N2- (3,5-Dimethyl-4-9.11 (1H, s), 8.19 (1H, d, J = methoxyphenyl) ) -N4- (2.2- 3.6 Hz), 7.69 (1H, d, J = 8.1 dimethyl-3-oxo-4H-5-997 Hz), 7.44 (1H, d, J = 8.4 Hz),? Irid [1,4] oxazin-6-yl) -5- + + 7.33 (2H, s), 3.68 (3H, s), fluoro-2,4-2.23 (6H, s), 1.53 (6H, s); Piirimidindiamine CLEM: purity: 99%; MS (m / e): 439 (MH +). T NMR (DEMO-d6): d 10.06 (1H, s), 9.85 (1H, s), N2- (3,5-Dimethyl-4- 8.25 (1H, d, J = 4.8 Hz), 7.33 (1H, s) d, J = 2.4 Hz), 7.24 (2H, methoxyphenyl) -N4- (3,4-ethyl phenyl) -5- s), 7.20 (1H, d, J = 2.7 Hz), 98 lendioxy 6.91 (1H, d , J = 8.4 Hz), 4.32 + fluoro-2,4-pyrimidindiamine (4H, s), 3.71 (3H, s), 2.25 (6H, s); LCMS: purity: 96.69%; MS (m / e): 397 (MH +).

No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d 9.88 (2H, broad s ), 8.26 (1H, d, J = 4.2 Hz), 7.64 (1H, N2- (3-Chloro-4-methoxy), 7.41 (1H, s), 7.30-7.28 5-methyphenyl) -N4- ( 3.4- (1H, m), 7.25-7.20 (1H, m), 999 ethylenedioxyphenyl) -5- 6.92 (1H, d, J = 10.2 Hz), + + + fluoro-2,4- 4.32 (4H, s), 3.79 (3H, s), pyrinimidine 2.29 (3H, s); LCMS: purity: 94.81%; MS (m / e): 417 (MH +). XH NMR (DEMO-d6): d N4- (3,4-Dihydro-2,2- 9.15 (1H, s), 9.08 (1H, s), dimethyl-4H-8.09 (lH, d, J = 3.6 Hz ), 8.04 benz [1,4] oxazin-6-yl) - (1H, d, J = 4.5 Hz), 7.45- 1000 5-fluoro-N2- [3- (N- 7.42 (2H, m), 7.17 (lH, t, J = + methylamin) carbonyl- 8.4 Hz), 7.01 (1H, d, J = 2.4 methylenexyphenyl) -2.4-Hz), 6.95 (lH, d, J = 8.4 Hz), pyrimidinediamine 6.65 ( lH, d, J = 8.7 Hz), 6.53 (lH, d, J = 9.3 Hz), 5.88 XH NMR (DEMO-d6): d 9.59 (1H, broad s), 8.17 N2- (3-Chloro-4-) methoxy-5-methylfeml) -N4- (3,4- (lH, d, J = 4.2 Hz), 7.65 (1H, s), 7.46 (1H, s), 6.94-6.86 dihydro-2,2-dimethyl- 1001 (2H, m), 6.68 (lH, d, J = 8.7 4H-benz [1,4] oxazin-6- + Hz), 3.77 (3H, s), 3.08 (2H, il) -5-fluoro- 2.4-s), 2.27 (3H, s), 1.34 (6H, s); pyriridinediamine purity: 94.5%; MS (m / e): 444 (M). XH NMR (DEMO-d6): d 9.06 (2H, s), 8.09 (lH, d, J = N4- (3,4-Dihydro-2.2- 3.6 Hz), 7.03 (lH, dd, J = 6.9 dimethyl-4H-Hz, J = 1.8 Hz), 6.95 (1H, benz [1,4] oxazin-6-yl) -dd, J = 8.1 Hz, J = 2.7 Hz), 1002 N2- (3.5- dimethoxyphenyl) -5- 6.63 (lH, d, J = 8.7 Hz), 6.11 (1H, s), 5.82 (1H, s), 3.71 fluoro-2,4- (6H, s), 3.07 (2H, s) , 1.34 pyridine diamine (6H, s); purity 95.9%; MS (T NMR (DEMO-dd): d 11.17 (1H, s), 9.27 (1H, s), N4- (2,2-Dimethyl-3- 9.24 (1H, s), 8.21 (1H, d, J = oxo-4H-5- 3.6 Hz), 7.67 (1H, m), 7.61? irid [1,4] oxazin-6-yl) -1003 (1H, d, J = 9 Hz), 7.52 (1H, 5 -fluoro-N2- (3- + + s), 7.44 (1H, d, J = 8.7 Hz), isopropylphenyl) -2.4- 7.19 (1H, t, J = 7.65 Hz), pmmidmdiamine 6.85 (lH, d , J = 7.8 Hz), 2.82 (lH, m), 1.53 (6H, s), 1.25 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt! H NMR (DMSO-d6): d 11.23 (1H, s), 10.12 (1H, s), N4- (2,2-Dimethyl-3-9.39 (1H, s), 8.27 (1H, d, J = oxo-4H-5- 4.8 Hz), 7.52 (1H, d, J = 6.9? Irid [1,4] oxazin-6-yl) - 1004 Hz), 7.43 (1H, d, J = 8.7 Hz), + 5-fluoro-N2- (2- 7.34-7.16 (4H,), 2.30 (3H, methylphenyl) -2.4-s), 1.50 (6H, s), purity pyrimidmdiamine 97.9%; MS (m / e): 395 (MH +). 1H NMR (DEMO-d6): d 2-Chloro-5-fluoro-N4- 8.43 (lH, d, J = 5.1 Hz), 7.57 methyl-N4- (3 -oxo-2,2,4- (lH, d, J = 8.4 Hz), 7.15 (1H, 1005 t rimethyl-5-dd, J = 8.1 Hz, J = 0.9 Hz), + pyrid [1,4] oxazin-6-yl) -3.59 (3H, s), 3.30 (3H, s), 4-pyrimidinamine 1.55 ( 6H, s); purity 97.2%; MS (m / e): 352 (MH +). 1 H NMR (DEMO-d 6): d 10.35 (1H, s), 8.47 (1H, d, J 2-Chloro-5-fluoro-N 4 - = 3.3 Hz), 7.62 (1H, d, J = (3-oxo -2,2,4-trimethyl-1006 8.7 Hz), 7.58 (1H, d, J = 8.4 5-pyrid [1,4] oxazin-6 Hz), 3.45 (3H, s), 1.55 (6H, ü ) -4-pyrimidmamine s); 96% purity; MS (m / e): 338 (MH +). 1 H NMR (DEMO-d 6): d 11.14 (1 H, s), 9.24 (1 H, s), N 4 - (2,2-Dimethyl-3- 9.19 (1 H, s), 8.21 (1 H, d, J = oxo -4H-5- 3.3 Hz), 7.76 (1H, d, J = 8.7 pyrid [1, 4] oxazin-6-yl) - 1007 Hz), 7.41 (lH, d, J = 8.7 Hz), + + 5 -fluoro-N2- (3,4,5- + 7.12 (2H, s), 3.75 (6H, s), trimethoxyphenyl) -2,4- 3.69 (3H, s), 1.52 (6H, s); pyrimidinediamine purity 96%; MS (m / e): 471 (MH +) X H NMR (DEMO-d 6): d 10.67 (1H, s), 9.40 (1H, s), N 2 - (3-Chloro-4-ethoxy-5- 9.20 (1H , s), 8.16 (1H, d, J = methylphenyl) -N4- (2.2-3.9 Hz), 7.74 (1H, d, J = 3 dimethyl-3-oxo-4H-1008 Hz), 7.45 (1H , d, J = 2.7 Hz), + + benz [1,4] oxazin-6-yl) - + 7.36 (1H, dd, J = 8.7 Hz, J = 5-fluoro-2,4-2.4 Hz), 7.25 (1H, d, J = 2.4 pyr ^ dindiamine Hz), 6.98 (lH, d, J = 8.7 Hz), 3.94 (2H, q, J = 7.2 Hz 1H NMR (DMSO-d6): d 9.62 (1H, s), 9.41 (1H, s), N2- (3-Chloro-4-methoxy- 8.27 (1H, s), 7.80 (1H, s), 5-methylphenyl) -5-fluoro- 7.73 (lH, d, J = 8.7 Hz), 7.48 N4- (3-oxo-2,2,4-1009 (1H, d, J = 8.7 Hz), 7.43 (1H, + + trimethyl-5 s), 3.78 (3H, d , J = 2.4 Hz), pyrid [1,4] oxazin-6-yl) -2.92 (3H, s), 1.55 (6H, d, J = 2,4-pyrimidinediamine 2.4 Hz), purity 97%, MS ( m / e): 473 (MH +).

No. Name of Compound Physical Data Tftase Triptase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 11.18 (1H, s) , 9.41 (1H, s), N2- (3-Chloro-4-ethoxy-5- 9.38 (1H, s), 8.23 (1H, d, J = methylphenyl) -N4- (2.2- 3.6 Hz), 7.74 (1H, d, J = 2.7 dimethyl-3-oxo-4H-5-1010 Hz), 7.61 (lH, d, J = 8.4 Hz), + pyrid [1,4] oxazin-6-yl) - 7.46 (lH, d, J = 8.1 Hz), 7.41 5-fluoro-2,4- (1H, d, J = 2.1 Hz), 3.95 (2H, pMmidindiamine q, J = 7.2 Hz), 2.27 (3H, s) , 1.53 (6H, s), 1.42 (1 H NMR (DMSO-d 6): d 10.74 (1H, s), 9.56 (1H, s), N 4 - (2,2-Dimethyl-3- 9.49 (1H, s) , 8.21-8.19 (2H, oxo-4H-m), 7.89 (2H, d, J = 9 Hz), benz [1,4] oxazin-6-yl) -1011 7.84 (2H, d, J = 9 Hz ), 7.37 5-fluoro-N2- [4- + + (oxazol-2-yl) fenu] -2,4- (1H, d, J = 0.6 Hz), 7.33 (1H, dd, J = 8.1 Hz, J = 2.4 Hz), pyrimidiamine 7.26 (lH, d, J = 2.7 Hz), 7.02 (1H, d, J = 8.7 Hz), 1.53 (1 H NMR (DMSO-d6): d 9.76 (1H, s), 9.74 (1H, s), 5-Fluoro-N2- [3 - 8.41 (1H, s), 8.32 (1H, d, J = (oxazol-2-yl) phenyl] -N4- 3.6 Hz), 8.25 (1H, s), 7.89- [3-oxo-2.2, 4-trimethyl-1012 7.83 (2H, m), 7.64 (1H, d, J 5-pyrid [1,4] oxazin-6- + = 7.8 Hz), 7.48 (1H, d, J = il] -2, 4- 7.8 Hz), 7.44 (1H, s), 7.36 pyrirm ^ indiamin (1H, d, J = 7.2 Hz), 3.42 (3H, s), 1.54 (6H, s), purity 96%, 1H NMR (DMSO -d6): d 9.76 (1H, s), 9.73 (1H, s), 5-Fluoro-N2- [4- 8.31 (lH, d, J = 3.6 Hz), 8.21 (oxazol-2-yl) phenyl] -N4- (lH, d, J = 0.9 Hz), 7.92 (2H, [3-oxo-2,2,4-trimethyl-1013 d, J = 9.3 Hz), 7.88 (2H, d, J 5-pyrid [1, 4] oxazin-6- = 9.6 Hz), 7.76 (1H, d, J = il] -2.4- 8.4 Hz), 7.54 (1H, d, J = 8.4 pyrimidinediamine Hz), 7.38 (lH, d, J = 0.9 Hz), 3.44 (3H, s), 1.57 (6H, 1H NMR (DMSO-d6): d N2- [3-Chloro-4-10.69 (1H, s), 9.43 (1H, s) , etoxic arbonylmethyl- 9.27 (1H, s), 8.17 (1H, d, J = enoxi-5-methylphenyl) - 3.6 Hz), 7.76 (1H, d, J = 2.7 1014 N4- (2,2-dimethyl-3-oxo - Hz), 7.46 (lH, d, J = 2.4 Hz), + + + 4H-benz [1,4] oxazin-6- 7.36 (1H, dd, J = 9 Hz, J = il) -5-fluoro -2.4- 2.7 Hz), 7.24 (1H, d, J = 2.4 pyrimidinediamine Hz), 6.99 (lH, d, J = 8.4 Hz), 4.58 (2H, s), 4.28 (2H, No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com ID, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 10.67 (1H, s), 9.53 ( 1H, s), N4- (2,2-Dimethyl-3- 9.38 (1H, s), 8.47 (1H, s), oxo-4H-8.20 (lH, d, J = 3.6 Hz), 8.04 benz [l , 4] oxazin-6-yl) -1016 (1H, s), 7.78 (1H, m), 7.58 + + 5-fluoro-N2- [3- (lH, s), 7.41 (lH, dd, J = 8.7 (oxazole-5-ü) phenyl] -2.4-Hz, J = 2.4 Hz), 7.35 (2H, d, pyrimidinediamine J = 4.8 Hz), 7.29 (1H, d, J = 2.4 Hz), 6.89 ( lH, d, J = 1H NMR (DMSO-d6): d 9.65 (1H, s), 9.57 (1H, s), 5-Fluoro-N2- [3- (oxazol-5-yl) phenyl] -N4- 8.47 (1H, s), 8.29 (1H, d, J = 3.6 Hz), 8.12 (1H, s), 8.84 [3-oxo-2,2,4-trimethyl-1017 (lH, d, J = 8.1 Hz), 7.74 (1H, 5-pyrid [1,4] oxazin-6), 7.62 (1H, s) , 7.43-7.32 il] -2.4- (3H,), 3.42 (3H, s), 1.54 pyrimidinediamine (6H, s); 96.4% purity; MS (m / e): 462 (MH +). 1 H NMR (DMSO-d 6): d N 2 - [3-Chloro-4-10.68 (1H, s), 9.41 (1H, s), cyclopentyloxy-5- 9.20 (1H, s), 8! 6 (lH, d , J = methylphenyl] -N4- (2.2- 3.6 Hz), 7.73 (1H, d, J = 2.7 1018 dimethyl-3-oxo-4H-Hz), 7.45 (lH, d, J = 2.4 Hz), benz [1,4] oxazin-6-yl) - 7.36 (1H, dd, J = 9 Hz, J = 5-fluoro-2.4-2.7 Hz), 7.24 (1H, d, J = 2.4 pyridine diamine Hz ), 6.98 (lH, d, J = 8.7 Hz), 4.65 (1H, m), 2.23 (3H, 1H NMR (DMSO-d6): d 10.72 (1H, s), 9.65 (1H, s), N4- (2,2-Dimethyl-3- 8.71 (1H, s), 8.27 (1H, t, J = oxo-4H- 1.2 Hz), 8.09 (lH, dd, J = 5.4 benz [1,4] oxazin-6 -il) - Hz, J = 0.9 Hz), 7.82 (1H, 1019 + + 5-fluoro-N4-methyl-N2- dd, J = 8.1 Hz, J = 0.9 Hz), [3- (oxazole-2- il) phenyl] - 7.60 (1H, d, J = 8.4 Hz), 2,4-? irimidmdiamine 7.48-7.43 (2H, m), 7.05-6.97 (2H, m), 6.87 (lH, d, J = 2.1 H 1 H NMR (DMSO-d 6): d N 4 - (2,2-Dimethyl-3-10.75 (1H, s), 9.56 (1H, s), 9.49 (1H, s), 8.43 (1H, s), oxo -4H- 8.20 (lH, d, J = 3.9 Hz), 7.83 benz [l, 4] oxazin-6-yl) -1020 (2H, d, J = 8.7 Hz), 7.59 (2H, + + 5-fluoro -N2- [ 4- (oxazole-5-ü) phenyl] -2,4-d, J = 8.7 Hz), 7.53 (1H, s), 7.33-7.28 (2H, m), 7.02 (1H, pijrimidindiapiine d, J = 8.4 Hz), 1.52 (6H, s); 97.4% purity; EM (m / e): No. Name of Compound Physical Data Triptase Triptase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 10.72 (1H, s), 9.72 (1H, s), N4- (2,2-Dimethyl-3- 8.20 (1H, d, J = 0.9 Hz), 8.11 oxo-4H-benz [1,4] oxazin-6-yl) - (1H, d, J = 5.7 Hz), 7.89 (4H, 1021 s), 7.38 (1H, d, J = 0.9 Hz), 5-fluoro-N4-methyl-N2- + [4- (oxazole-2 -yl) phenyl] -7.07-6.97 (2H,), 6.87 (1H, d, J = 2.7 Hz), 3.54 (3H, s), 2,4-pyriridinediamine 1.52 (6H, s); purity 97.1%; MS (m / e): 461 (MH +). 1022 + N4- (2,2-Dimethyl-3-10.71 (1H, s), 9.55 (1H, s), 8.50 (1H, s), 8.37 (1H, s), oxo-4H-benz [1,4] oxazin -6-il) - 8.08 (lH, d, J = 5.7 Hz), 7.68 1023 5-fluoro-N4-methyl-N2- (lH, d, J = 8.1 Hz), 7.66 (1H, + + s), 7.43-7.34 (2H, m), 7.05- [3- (oxazol-5-yl) phenyl] -6.97 (2H,), 6.87 (1H, d, J, 2,4-pyrimidinediamine = 2.4 Hz), 3.55 (3H , s), 1.51 (6H, s); purity 95.6%; MS 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 -methyl-N 2 - 9.71 (1H, s), 8.20 (lH, d, J = 0.9 Hz), 8.10 (1H, d, J = 6 [4 - (oxazol-2-yl) phenyl] - Hz), 7.90 (4H, s), 7.38 (1H, N4- (3-oxo-2,2,4-1024 d, J = 0.6 Hz), 7.27 (1H , s), trimethylbenz [1,4] oxazin + 7.09 (2H, s), 3.59 (3H, s), -6-yl) -2.4-3.34 (3H, s), 1.52 (6H, s); pyrimidinediamine purity 97.4%; MS (m / e): 475 (MH +). 1 H NMR (DMSO-d 6): d 5-Fluoro-N 4 -methyl-N 2 - 9.65 (1H, s), 8.72 (1H, d, J = 1.8 Hz), 8.27 (1H, d, J = 0.6 [3- (oxazol-2-yl) phenyl] - Hz), 8.08 (1H, d, J = 6Hz), N4- (3-oxo-2,2,4-1025 7.83-7.79 (1H, m), 7.60 (1H , + + trimethylbenz [1,4] oxazin d, J = 7.2 Hz), 7.47 (lH, d, J -6-il) -2,4- = 7.8 Hz), 7.43 (1H, d, J = pyrimidmdiamine 0.9 Hz), 7.28 (1H, s), 7.07 (2H, s), 3.62 (3H, s), 3.35 No. Compound Name Physical Data Triptase Tftase Triptase f syk Com LD, LD, LD, Lpt CMC, CMC, CMC , IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.60 (1H, s), 8.44 (1H, s), 5-Fluoro-N4-methyl-N2- 8.07 (1H, d, J = 6 Hz), 7.88 [4- (oxazol-5-yl) phenyl] - (2H, d, J = 8.4 Hz), 7.65 (2H, N4- (2,2,4-trimethyl-3-1026 d, J = 8.7 Hz), 7.57 (1H, s), + oxo-benz [1,4] oxazin- 7.27 (1H, s), 7.08 (2H, s), 6-yl) -2.4- 3.58 (3H , s), 3.34 (3H, s), pyrimidinediamine 1.52 (6H, s); purity 98.61%; MS (m / e): 475 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3-Chloro-4-11.18 (1H, s), 9.38 (1H, s), cyclopentyloxy-5- 9.35 (lH, s), 8.22 (lH, d, J = methylphenyl) -N4- (2.2- 3.6 Hz), 7.74 (1H, d, J = 2.4 1027 dimethyl-3-oxo-4H-5 Hz), 7.61 (lH, d, J = 8.7 Hz), pyrid [1,4] oxazin-6-yl) - 7.46 (lH, d, J = 8.4 Hz), 7.41 5-fluoro-2,4- (1H, d, J = 2.7 Hz), 4.67 (1H, pyrimidinediamine m), 2.26 (3H, s), 2.00-1.60 (8H, m), 1.53 (6H, s) 1H NMR (DMSO-d6): d 11.18 (1H, s), 9.60 (1H, s), N4- (2,2-Dimethyl-3- 9.37 (1H, s), 8.38 (1H, s), 8.27 (2H, m), 7.93 (1H, d, J pyrid [1,4] oxazin-6-yl) - 1028 = 8.4 Hz), 7.71 (1H, d, J = 5-fluoro-N2- [3- + + 8.7 Hz), 7.60 (1H, d, J = 8.1 (oxazol-2-yl) phenyl] -2, 4- Hz), 7.44-7.34 (3H,), 1.53 pyridine diamine (6H, s); 95% purity; MS (m / e): 448 (MH +). 1 H NMR (DMSO-d 6): d 11.17 (1H, s), 9.45 (1H, s), N 4 - (2,2-Dimethyl-3- 9.31 (1H, s), 8.54 (2H, dd, J oxo- 4H-5- = 9.9 Hz, J = 0.9 Hz), 8.24 pyrid [1,4] oxazin-6-yl) -1029 5-fluoro-N2- [3- (1H, d, J = 3.6 Hz), 8.10 (1H, + s), 7.78-7.72 (2H, m), 7.42- (oxazole-4-ü) phenyl] -2.4- 7.29 (3H, m), 1.52 (6H, s); pmmid diamine purity 96.4%; MS (m / e): 448 (MH +). 1 H NMR (DMSO-d 6): d 9.47 (1H, s), 8.59 (1H, s), 5-Fluoro-N 4 -methyl-N 2 - 8.51 (1H, s), 8.41 (1H, s), [3- (oxazol-4-yl) phenyl] -8.05 (1H, d, J = 5.4 Hz), 7.66 N4- (3-oxo-2,2,4- (1H, d, J = 7.5 Hz), 7.41-1030 trimethylbenz [1,4] oxazin 7.32 (2H, m), 7.27 (1H, s), + + -6-yl) -2.4-7.07 (2H, s), 3.60 (3H, s), pyrimidine diamine 3.35 ( 3H, s), 1.51 (6H, s); 97.4% purity; MS (m / e): 475 (MH +).

No. Name of Compound Physical Data Tftase Triptase Triptase f syk Com ID, ID, ID, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 9.60 (1H, s) , 8.44 (1H, s), 5-Fluoro-N4-methyl-N2- 8.07 (1H, d, J = 6 Hz), 7.88 [4- (oxazol-5-yl) phenyl] - (2H, d, J = 8.4 Hz), 7.65 (2H, N4- (2,2,4-trimethyl-3-1026 d, J = 8.7 Hz), 7.57 (1H, s), + oxo-benz [1, 4] oxazin- 7.27 (1H, s), 7.08 (2H, s), 6-yl) -2.4- 3.58 (3H, s), 3.34 (3H, s), piri idindiamina 1.52 (6H, s); purity 98.61%; MS (m / e): 475 (MH +). 1 H NMR (DMSO-d 6): d N 2 - (3-Chloro-4-11.18 (1H, s), 9.38 (1H, s), cyclo-entyloxy-5- 9.35 (1H, s), 8.22 (1H, s) , J = methylphenyl) -N4- (2.2- 3.6 Hz), 7.74 (1H, d, J = 2.4 1027 dimethyl-3-oxo-4H-5 Hz), 7.61 (lH, d, J = 8.7 Hz ), +? irid [1,4] oxazin-6-yl) - 7.46 (lH, d, J = 8.4 Hz), 7.41 5-fluoro-2,4- (1H, d, J = 2.7 Hz), 4.67 (1H, pyrimidmdiamine m), 2.26 (3H, s), 2.00-1.60 (8H, m), 1.53 (6H, s) 1H NMR (DMSO-d6): d 11.18 (1H, s), 9.60 (1H, s) ), N4- (2,2-Dimethyl-3- 9.37 (1H, s), 8.38 (1H, s), oxo-4H-5- 8.27 (2H, m), 7.93 (1H, d, J? Irid [ 1, 4] oxazin-6-yl) -1028 = 8.4 Hz), 7.71 (1H, d, J = 5-fluoro-N2- [3- + 8.7 Hz), 7.60 (1H, d, J = 8.1 (oxazole -2-yl) phenyl] -2.4-Hz), 7.44-7.34 (3H, m), 1.53 pyridine diamine (6H, s); 95% purity; MS (m / e): 448 (MH +). 1 H NMR (DMSO-d 6): d 11.17 (1H, s), 9.45 (1H, s), N 4 - (2,2-Dimetü-3- 9.31 (1H, s), 8.54 (2H, dd, J oxo- 4H-5- = 9.9 Hz, J = 0.9 Hz), 8.24 pyrid [1,4] oxazin-6-yl) -1029 (lH, d, J = 3.6 Hz), 8.10 (1H, + 5-fluoro-N2 - [3 s), 7.78-7.72 (2H, m), 7.42- (oxazol-4-yl) phenyl] -2.4- 7.29 (3H,), 1.52 (6H, s); pyrir ^ indiamina purity 96.4%; MS (m / e): 448 (MH +). 1 H NMR (DMSO-d 6): d 9.47 (1H, s), 8.59 (1H, s), 5-Fluoro-N 4 -methyl-N 2 - 8.51 (1H, s), 8.41 (1H, s), [3- (oxazol-4-yl) phenyl] -8.05 (lH, d, J = 5.4 Hz), 7.66 N4- (3-oxo-2,2,4- (1H, d, J = 7.5 Hz), 7.41-1030 + trimethylbenzf 1, 4] oxazin 7.32 (2H, m), 7.27 (1H, s), -6-yl) -2.4-7.07 (2H, s), 3.60 (3H, s), pyrinindianamine 3.35 (3H, s), 1.51 (6H, s); 97.4% purity; MS (m / e): 475 (MH +).

No. Name of Compound Physical Data Triptase Tftase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- (3.5 -Dimethyl-4-9.11 (1H, s), 8.00 (1H, J = methoxyphenyl) -5-fluoro- 5.7 Hz), 7.42 (2H, s), 7.24 N4-methyl-N4- (3-oxo- (1H , s), 7.05 (2H, s), 3.68 1031, 2,2,4-trimethyl- + (3H, s), 3.55 (3H, s), 3.33, benz [1,4] oxazin-6-yl) - ( 3H, s), 2.25 (6H, s), 1.51 2,4-pyrimidinediamine (6H, s); 97.84% purity; MS (m / e): 466 (M). 1 H NMR (DMSO-d 6): d 9.49 (1H, s), 8.07 (1H, dd, J N 2 - (3-Chloro-4- = 6 Hz, J = 1.5 Hz), 7.81 cyclopentyloxy-5-methylphenyl) - 5-fluoro- (1H, d, J = 2.7 Hz), 7.47 (1H, d, J = 2.4 Hz), 7.27 (1H, s), 1032 N4-methyl-N4- (3-oxo-7.07 (2H, s), 4.69 (1H, m), 2,2,4-trimethyl-3.61 (3H, s), 3.33 (3H, s), benz [1,4] oxazin-6-yl) - 2.29 (3H, s ), 2.0-1.6 (8H,), 2,4-pyrirmdmdiamine 1.51 (6H, s); purity 96.15% 1H NMR (DMSO-d6): d 9.49 (lH, d, J = 0.9 Hz), 9.15 N2- (3,5-Dimetü-4- (1H, s), 8.21 (1H, d, J = 3.6 methoxyphenyl) -5-fluoro-Hz), 7.81 (lH, d, J = 8.7 Hz), N4- (3-oxo-2,2,4-1033 7.45 (lH, d, J = 8.4 Hz), 7.35 + + trimethyl- (2H, s), 3.69 (3H, s), 3.43 benz [1, 4] oxazin-6-yl) - (3H, s), 2.23 (6H, s), 1.54 2,4-pyrirm 'dindiamine (6H, s); purity 98.82%; MS (m / e): 453 (M). 5 1 H NMR (DMSO-d 6): d N 2 - (3-Chloro-4-9.63 (1H, s), 9.40 (1H, s), cyclopentyloxy-5- 8.26 (lH, d, J = 3.6 Hz), 7.78 methylphenyl) -5-fluoro- (1H, d, J = 2.4 Hz), 7.72 (1H, 1034 N4- (3-oxo-2,2,4-d, J = 8.4 Hz), 7.48 (lH, d, J trimethyl- = 8.4 Hz), 7.41 (1H, d, J = benz [1,4] oxazin-6-yl) - 2.4 Hz), 4.68 (1H, m), 3.41 2,4-? Irimidindiamine (3H, s), 2.26 (3H, s), 1.95-1.60 (8H, m), 1.54 (6H, s); 1 H NMR (DMSO-d 6): d 11.23 (1H, s), 9.70 (1H, s), or N 4 - (2,2-Dimetü-3-9.53 (1H, s), 8.27 (lH, d, J = 3.6 Hz), 8.20 (1H, d, J = 0.9? Irid [1,4] oxazin-6-yl) -1035 Hz), 7.90 (2H, d, J = 9.3 Hz), 5-fluoro-N2- [ 4-8.86 (2H, d, J = 9.5 Hz), 7.55 (oxazol-2-yl) phenyl] -2.4- (lH, d, J = 8.4 Hz), 7.51 (1H, pyrimidinediamine d, J = 8.4 Hz), 7.37 (1H, J = 0.9 Hz), 1.56 (6H, s No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 10.65 (1H, s ), 9.41 (1H, d, J N4- (2,2-Dimethyl-3- = 1.2 Hz), 9.32 (1H, s), 8.50 oxo-4H- (1H, d, J = 0.6 Hz), 8.47 ( 1H, benz [1,4] oxazin-6-yl) -1036 s), 8.17 (1H, d, J = 3.9 Hz), 5-fluoro-N2- [3- + + (oxazol-4-yl) phenyl ] -2.4- 8.08 (1H, s), 7.78 (1H, d, J = 8.7 Hz), 7.43 (lH, dd, J = 8.7 pyrimidindiainine Hz, J = 2.4 Hz), 7.39-7.27 (3H,) , 6.88 (1H, d, J 1 H NMR (DMSO-d 6): d N 2 - [3-Chloro-5-methyl-4-11.19 (1H, s), 9.43 (2H, s), (N-methylamino) - 8.24 (lH, d, J = 7.8 Hz), 8.18 carbonylmethyl- (lH, d, J = 4.5 Hz), 7.78 (1H, enoxyphenyl) -N4- (2.2-1037 d, J = 2.4 Hz), 7.60 (1H, d, J dimethyl-3-oxo-4H-5- + = 8.4 Hz), 7.47 (1H, d, J =? Irid [1,4] oxazin-6-yl) - 8.4 Hz), 7.43 ( 1H, d, J = 2.4 5-fluoro-2,4-Hz), 4.32 (2H, s), 2.79 (3H, pd ± mdindiamine d, J = 4.8 Hz), 2.29 (3H 1H NMR (DMSO-d6) : d N2- (3,5-Dimethyl-4-11.18 (1H, s), 9.26 (1H, s ), ethoxycarbonyl- 9.16 (1H, s), 8.19 (lH, d, J = methyleneoxyphenyl) -N4- 3.3 Hz), 7.68 (1H, d, J = 8.4 1038 (2,2-dimethyl-3-oxo-4H - Hz), 7.46 (lH, d, J = 8.4 Hz), + 5-pyrid [1, 4] oxazin-6- 7.33 (2H, s), 4.49 (2H, s), ü) -5-fluoro- 2.4- 4.28 (2H, q, J = 7.2 Hz), 2.23 piirir dmadiamine (6H, s), 1.52 (6H, s), 1.33 (3H, t, J = 7.2Hz), pur 1H NMR (DMSO- d6): d N2- (3-Chloro-4- 10.72 (1H, s), 9.68 (1H, s), isopropoxy-5-9.44 (1H, s), 8.20 (1H, d, J = methylphenyl) -N4 - (2.2- 3.6 Hz), 7.70 (1H, d, J = 2.1 1039 dimethyl-3-oxo-4H-Hz), 7.42 (lH, d, J = 2.4 Hz), + benz [l, 4] oxazin-6-yl) - 7.35 (1H, dd, J = 8.7Hz, J = 5-fluoro-2,4- 2.4 Hz), 7.24 (1H, d, J = 2.4 pyrimidinediamine Hz), 6.98 (lH, d , J = 8.4 Hz), 4.36 (1H, quint, J = 1H NMR (DMSO-d6): d N2- (3-Chloro-4-11.17 (1H, s), 9.37 (1H, s), isopropoxy-5 - 9.35 (1H, s), 8.22 (lH, d, J = methylphenyl) -N4- (2.2- 3.0 Hz), 7.74 (1H, d, J = 2.7 1040 dimethyl-3-oxo-4H-5- Hz), 7.61 (lH, d, J = 8.7 Hz), + pyrid [1,4] oxazin-6-yl) - 7.45 (lH, d, J = 8.7 Hz), 7.41 5-fluoro-2,4- (1 HOUR, d, J = 2.7 Hz), 4.36 (1H, pyrimidiamine quint, J = 6.0 Hz), 2.25 (3H, s), 1.52 (6H, s), 1.

No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com ID, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- [3.5 -Dimethyl-4- (N- 11.18 (1H, s), 9.28 (1H, s), methyamin) carbonyl- 9.18 (1H, s), 8.19 (2H, d, J = methyleneoxyphenyl) -N4- 3.6 Hz), 7.68 (1H, d, J = 8.4 1041 (2,2-dimethyl-3-oxo-4H-Hz), 7.45 (lH, d, J = 8.7 Hz), + 5-pyrid [1,4] oxazin-6 - 7.34 (2H, s), 4.22 (2H, s), il) -5-fluoro-2,4- 2.79 (3H, d, J = 4.5 Hz), 2.23 pyrir dinambine (6H, s), 1.52 (6H , s); 98% purity; MS (m / e): 496 (MH 1 H NMR (DMSO-d 6): d N 2 - (3-Chloro-4-11.19 (1H, s), 9.42 (2H, s), ethoxycarbonyl-8.23 (lH, d, J = 3.6 Hz), 7.76 methyleneoxy-5-methylphenyl) -N4- (2.2- (1H, d, J = 2.4 Hz), 7.60 (1H, 1042 d, J = 8.4 Hz), 7.47 (lH, d , J dimethyl-3-oxo-4H-5- = 8.4 Hz), 7.42 (1H, d, J = pyrid [1,4] oxazin-6-yl) - 2.1 Hz), 4.60 (2H, s), 4.27 5-fluoro-2,4- (2H, q, J = 7.2 Hz), 2.29 (3H, pyrimidinediamine s), 1.52 (6H, s), 1.33 (N2- [3-Chloro-4- [N- 1H NMR (DMSO-d6): d (2.3-11.17 (1H, s), 9.42 (1H, s), djTddroxypropyl) arnino] 9.40 (1H, s), 8.23 (1H, d, J = carbonylmethyleneoxy-5-3.6 Hz), 7.98 (1H, t, J = 5.7 1043 methylphenyl) -N4- (2.2-Hz), 7.78 (1H, d, J = 2.7 Hz), + + dimethyl-3-oxo-4H-5- 7.61 (lH, d, J = 8.7 Hz), 7.47 pyrid [1,4] oxazin-6-yl) - (1 H, d, J = 8.4 Hz), 7.34 (1 H, 5-fluoro-2,4-d) , J = 1.8 Hz), 4.94 (1H, broad pyrimidinediamine s), 4.67 (1H, broa 1H NMR (DMSO-d6): d N2- [3,5-Dimethyl-4- (N- 11.18 (1H, s) , 9.27 (1H, s), cyclopentylamino) -9.17 (1H, s), 8.19 (lH, d, J = carbonylmethylenexyphenyl) -N4 - (2,2-di ethyl- 3.6 Hz), 8.03 (1H, d, J = 7.8 1044 Hz), 7.67 (lH, d, J = 8.7 Hz), 7.45 (lH, d, J = 8.7 Hz), 7.34 pyrid [1, 4] oxazin-6-yl) - (2H, s), 4.23 (1H, m), 4.21 5-fluoro-2,4- (2H, s), 2.23 (6H, s), 1.91 pyrimidindiamiria (2H, m), 1.76 (2H, m), 1. 1H NMR (DMSO-d6): d chloride salt 12.12 (1H, s), 9.95 (1H, s), hydrogen of N4- (2, 2- 9.58 (1H, s), 8.26 (lH, d, J = Difluoro-3-oxo-4H-3.6 Hz), 8.06 (1H, d, J = 4.2 benz [1,4] oxazin-6-yl) - 1045 Hz), 7.65 (lH, d, J = 2.1Hz), 5-fluoro-N2- [3- (N- + 7.61 (lH, d, J = 2.4 Hz), 7.41 methyamin) carbonyl- (1H, s), 7.35 (1H, d, J = 8.7 methylenexyphenyl) -2.4-Hz), 7.30 (lH, d, J = 9.0 Hz), pyrimidinediamine 7.21 (lH, t, J = 7.8 No. Compound Name Data Physics Tftase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d Acid salt 12.05 (1H, s), 9.81 ( 1H, s), methanesulfonic of N4- 9.38 (1H, s), 8.24 (lH, d, J = (2,2-Difluoro-3-oxo- 3.6 Hz), 8.04 (1H, d, J = 4.2 4H- benz [1, 4] or xazin-6- 1046 Hz), 7.66 (1H, dd, J = 10.5 il) -5-fluoro-N2- [3- (N-Hz, J = 1.5 Hz), 7.51 (1H, d, methyamin) carbonyl- J = 1.8 Hz), 7.43 (1H, s), metüenoxifeniTJ-2,4-7.37-7.29 (2H, m), 7.19 (1H, pyrimidinepnamine tt, J = 7.8 Hz), 6.59 (lH, d, 1H NMR ( DMSO-d6): d Acid salt 10.74 (1H, s), 10.11 (1H, s), methanesulfonic acid of N4- 9.82 (1H, s), 8.26 (lH, d, J = (2,2-Dimethyl-3 -oxo- 4.5 Hz), 8.05 (1H, s), 7.88 1047 4H-benz [1, 4] oxazin-6- (1H, s), 7.71 (1H, d, J = 8.4 il) -5-fluoro- N2-Hz), 7.45 (1H, dd, J = 9.0 (indazol-6-yl) -2.4-Hz, J = 2.7 Hz), 7.31 (1H, pyrimidinediamine dd, J = 8.7 Hz, J = 1.5 Hz ), 7.24 (lH, d, J = 2.4 Hz), 6.97 1 H NMR (DMSO-d6): d 10.73 (1H, s), 9.282 (1H, s), chloride salt of 9.60 (1H, s), 8.24 (1H, d, J = hydrogen of N4- (2.2-4.2 Hz), 8.02 (2H, s), 7.67 Dimethyl-3-oxo-4H- (lH, d, J = 8.4 Hz), 7.47 (1H , 1048 benz [1,4] oxazin-6-yl) -d, J = 8.7 Hz), 7.36-7.33 + 5-fluoro-N2- (indazole- (2H, m), 6.98 (lH, d, J = 8.7 6-il) -2.4-Hz), 1.49 (6H, s); purity pirirnidindiamiTia 99.3%; MS (m / e): 420 (MH +). 1 H NMR (DMSO-d 6): d 11.21 (1H, s), 9.56 (1H, s), N 4 - (2,2-Dimethyl-3- 9.40 (1H, s), 8.29 (lH, d, J = oxo -4H-5- 3.6 Hz), 8.11 (1H, s), 7.96? Irid [1, 4] oxazin-6-yl) -1049 (1H, s), 7.71 (1H, d, J = 7.2 + N2- (l-ethylindazol-6-yl) - Hz), 7.64 (lH, d, J = 9.0 Hz), 5-fluoro-2,4- 7.46 (lH, d, J = 8.4 Hz), 7.36 pyrimidinediamine (1H, dd, J = 8.7 Hz, J = 1.5 Hz), 4.25 (2H, q, J = 7. 1H NMR (DMSO-d6): d N4- (2,2-Dimethyl-3-11.22 (1H, s), 9.56 (1H, s), oxo-4H-5-9.41 (1H, s), 8.29 (lH, d, J =? irid [1,4] oxazin-6-yl) - 3.3 Hz), 8.15 (1H, s), 7.96 1050 N2- (l- (1H, s), 7.70 (1H, d, J = 8.4 + isopropylindazol-6-yl) - Hz), 7.63 (1H, d, J = 8.4 Hz), 5-fluoro-2 , 4- 7.46 (lH, d, J = 8.7 Hz), 7.35 pyrimidindiarnine (1H, dd, J = 8.7 Hz, J = 1.2 Hz), 4.63 (1H, quint, J No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, LD, LD, llpt CMC, CMC, CMC, IE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 2-Chloro-N4- (3.4- 9.84 (1H, s ), 8.35 (1H, d, J = dihydro-2,2-dimethyl- 3.3 Hz), 7.09 (1H, d, J = 8.1 1051 4H-5-pyrid [1,4] oxazin-Hz), 7.06 (1H , d, J = 8.1 Hz), 6-yl) -5-fluoro-4-6.79 (1H, s), 3.23 (2H, s), pyridine-amylamine 1.36 (6H, s); purity 96.73%; MS (m / e): 310 (MH +). 1 H NMR (DMSO-d 6): d 9.50 (1H, s), 8.94 (1H, s), N 4 - (3,4-Dihydro-2,2- 8.21 (lH, d, J = 3.6 Hz), 8.17 dimethyl. -4H-5- (1H, s), 7.93 (1H, s), 7.63 pyrid [1,4] oxazin-6-yl) -1052 (lH, d, J = 8.7 Hz), 7.35 (1H, + + 5-fluoro-N2- (l- + d, J = 1.5 Hz), 7.30 (lH, d, J methuindazol-6-yl) -2.4- = 7.8 Hz), 7.01 (1H, d, J = pyrimidinediamine 8.4 Hz), 6.72 (1H, s), 3.92 (3H, s), 3.24 (2H, d, J = 2. 1H NMR (DMSO-d6): d N4- (3,4-Dihydro-2,2- 9.29 (1H, s), 8.83 (1H, s), dimethyl-4H-5-8.15 (lH, d, J = 3.6 Hz), 8.03 pyrid [1,4] oxazin-6-yl) - (1H, m ), 7.47 (lH, t, J = 2.1 1053 5-fluoro-N2- [3- (N-Hz), 7.40 (lH, d, J = 7.5 Hz), + methyamin) carbonyl- 7.34 (lH, d, J = 6.9 Hz), 7.20 methylenexyphenyl] -2.4- (1H, t, J = 8.4 Hz), 7.02 (1H, pyrimidinediamine d, J = 8.1 Hz), 6.67 (lH, s), 6.56 (lH, dd , J = 7.8 1 H NMR (DMSO-d 6): d N 2 - [3-Chloro-4- (N-11.19 (1H, s), 9.70 (1H, s), methylamino) carbonyl- 9.52 (1H, s), 8.28 (1H, d, J = phenyl] -N4- (2,2-dimethyl-2.4 Hz), 8.21 (1H, d, J = 5.1 1054 3-oxo-4H-5 Hz), 7.97 (1H, s ), 7.62-7.57 + + pyrid [1, 4] oxazin-6-yl) - (2H, m), 7.50 (lH, d, J = 9.0 5-fluoro-2,4-Hz), 7.34 (lH, d, J = 8.4 Hz), pyrirm ^ indiamine 2.81 (3H, d, J = 3.6 Hz), 1.53 (6H, s); purity 99.5% 1H NMR pMSO-d6): d N4- (2,2-Dimethyl-3- 11.12 (1H, s), 9.25 (1H, s), 9.12 oxo-4H-5- (1H, s), 8.17 (1H, d, J = 3.3 Hz), pyrid [1,4] oxazin-6-yl) - 7.64 (1H, d, J = 8.4 Hz), 7.43 1055 N2- (3.4- + (1H, d , J = 8.4 Hz), 7.35 (1H, d, ethylenedioxyphenyl) -5- J = 2.4 Hz), 7.10 (1H, dd, J = 9.0 fluoro-2.4-Hz, J = 2.4 Hz), 6.76 (1H , d, J = pyrimidmdiamine 9.0 Hz), 4.26 (4H, m), 1.53 (6H, lHNMR (DMSO-d6): d chloride salt of 11.23 (1H, s), 9.88 (1H, s), 9.28 hydrogen N4- (2.2- (1H, s), 8.33 (1H, d, J = 3.6 Hz), Dimethyl-3-oxo-4H-5- 8.02 (lH, s), 7.98 (lH, s), 7.66 1056 pyrid [1,4] oxazin-6-yl) - + (2H, t, J = 8.4 Hz) .7.45 (1H, d, 5-fluoro-N2- [l- J = 8.4 Hz), 7.31 (lH , dd, J = methylindazol-6-yl] -2.4- 8.4 Hz, J = 1.5 Hz), 3.93 (3H, s), pmptid diamine 1.53 (6H, s), purity 100%, MS No. Name of Compound Physical Data Triptase Triptase Tftasa f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d P-11.23 acid salt (1H, s ), 9.81 (2H, s), tol sulfonium of N4- 8.32 (lH, d, J = 3.9 Hz), 8.02 (2,2-Dirnethyl-3-oxo- (1H, s), 7.98 (1H, s), 7.67 1057 4H-5-pyrid [l , 4] oxazin- (2H, t, J = 8.7 Hz), 7.55 (2H, + 6-yl) -5-fluoro-N2- [l- d, J = 7.8 Hz), 7.44 (lH, d, J methylindazol-6-yl] -2.4- = 8.4 Hz), 7.31 (1H, dd, J = pijrimidindiamine 8.4 Hz, J = 0.9 Hz), 7.19 (2H, d, J = 8.4 Hz), 3.94 (3 1H NMR (DMSO-d6): d Acid salt 11.22 (1H, s), 9.76 (1H, s), methanesulfonic acid of N4- 9.72 (lH, s), 8.31 (1H, d, J = (2,2-Dimethyl) -3-oxo- 3.3 Hz), 8.04 (1H, s), 7.97 1058 4H-5-pyrid [1,4] oxazin- (1H, s), 7.67 (2H, d, J = 8.4 + 6-yl) -5-fluoro-N2- [l-Hz), 7.45 (1H, d, J = 8.1 Hz), methylindazol-6-yl] -2.4-3.32 (lH, d, J = 8.4 Hz), 3.93 piirimidm diamine (3H, s), 2.41 (3H, s), 1.53 (6H, s); 99% purity; MS 1 H NMR (DMSO-d 6): d 2.13 (s, 6H), 3.58 (s, 3H), 4.62 (s, 2H), 7.22 (s, 2H), 1059 + CLEM: ret time: 10.29 mia .; purity: 97.75%; MS (me): 411.18 (MH +) T NMR (CDC13): d 1.45 (s, 6H), 2.13 (s, 3H), 6.78 (m, N4- (2,2-Dimethyl-3- 3H), 6.90 ( d, J = 7.5 Hz, 1H), oxo-4H-7.04 (t, J = 8.1 Hz, 1H), 7.27 benz [1, 4] oxazin-6-yl) - (s, 1H), 7.74 (d, J = 5.1 Hz, 1060 5-fluoro-N2- (3-1H), 7.91 (s, 1H), 9.09 (s, + hydroxy-2-methylphenyl) -1H), 10.86 (s, 1H); 19F - 162.90; LCMS: ret time: 8.06 min X H NMR (DMSO-d 6): d 1.99 (s, 3 H), 3.79 (s, 3 H), 4.60 (s, 5-Fluoro-N 2 - (3 2 H), 6.54 (d , J = 7.8 Hz, 1H), methoxy-2-methylphenyl) - 6.78 (d, J = 8.1 Hz, 1H), 6.98 1061 N4- (3-oxo-2H, 4H-5- (dd, J = 2.4 and 8.1 Hz, 1H), + pyridfl, 4] oxazin-6-yl) - 7.12 (t, J = 8.4 Hz, 1H), 7.44 2,4-? Mmidmdiamine (d, J = 8.7 Hz, 1H), 8.03 ( d, J = 3.9 Hz, 1H), 8.73 (s, 1H), 9.23 (s, lH), 11.08 No. Compound Name Physical Data Triptase Triptase Triptase f syk Com ID, ID, ID, llpt CMC, CMC, CMC , IgE, 3pt IgE, 8pt Ion, 3? T Tí NMR (CDC13): d 1.49 (s, 6H), 2.12 (s, 3H), 3.95 (s, N4- (2,2-Dimethyl-3- 3H) , 6.71 (dd, J = 2.1 and 8.4 oxo-4H-Hz, 1H), 6.79 (d, J = 8.4 Hz, benz [1,4] oxazin-6-yl) -1062 1H), 6.89 (d, J = 7.8 Hz, 1H), + 5-fluoro-N2- (3-6.98 (d, J = 8.4 Hz, 1H), 7.26 methoxy-2-methylphenyl) - (m, 3H), 7.66 (d, J = 4.2 Hz, 2,4-pipithidmdiarnine 1H), 7.93 (s, 1H), 11.04 (s, 1H); 19F NMR (282 MHz, XH NMR (CDC13): d 2.02 (s, 3H), 4.48 (s, 2H), 6.72 (m, 5-Fluoro-N2- (3- 2H), 6.82 (m, 1H), 6.96 (t, J = hydroxy-2-methylphenyl) - 8.1 Hz, 1H), 7.25 (m, 1H), 1063 N4- (3-oxo-2H, 4H-5-79.79 (d, J = 4.8 Hz, 1H ); + pyrid [1,4] oxazin-6-yl) -MSCM: ret time: 7.10 2,4-pyrimidiamine min, purity: 77.55%, MS (m / e): 383.14 (MH +). (CDC13): d 1.41 (s, 6H), 2.04 (s, 3H), 6.61 (t, J = N4- (2,2-Dimethyl-3- 4.5 Hz, 1H), 6.94 (m, 3H), oxo -4H-5-7.58 (d, J = 8.7 Hz, 1H), 7.77? Irid [1,4] oxazin-6-yl) -1064 (d, J = 3.9 Hz, 1H), 19F + 5-fluoro- N2- (3-NMR (282 MHz, CDC13): d-hydroxy-2-methylphenyl) - -165.40; LCMS: ret time: 2,4-pyrimidinediamine 7.83 min, purity: 99.01%, MS (m / e): 411.19 (MH +). T NMR (CDC13): d 1.57 (s, 6H), 2.19 (s, 3H), 3.88 (s, N4- (2,2-Dimethyl-3- 3H), 6.79 (dd, J = 2.1 and 7.2 oxo-4H-5 Hz, 1H), 7.05 (d, J = 8.7 Hz, pyrid [1,4] oxazin-6-yl) -1H), 7.17 (m, 2H), 7.70 (d, 1065 + 5-fluoro-N2- (3- J = 8.7 Hz, 1H), 7.85 (d, J = methoxy-2-methylphenyl) - 3.6 Hz, 1 HOUR); 19 F NMR (282 2,4-p-methylindiamine MHz, CDC13): d-161.49; LCMS: time ret .: 10.92 min; purit T NMR (CDC13): d 1.49 (s, N4- (2,2-Dimethyl-3-6H), 2.26 (s, 3H), 3.80 (s, oxo-4H-3H), 4.84 (s, 2H) , 6.69 (dd, benz [1,4] oxazin-6-yl) -5-fluoro-N2- [3- J = 2.4 and 8.4 Hz, 1H), 6.82 (d, 1066 J = 8.7 Hz, 1H), 6.86 (d, J = methoxycarbonyl- + 8.1 Hz, 1H), 6.98 (d, J = 8.1 methyleneoxy-2 Hz, 1H), 7.19 (t, J = 8.1 Hz, methylphenyl) -2,4- 1H), 7.26 (s, 1H), 7.46 (s, pyrimidinediamine 1H), 7.72 (s, 1H), 7.79 No. Compound Name Physical Data Triptase Tftasa Tftasa f syk Com LD, ID, ID, llpt CMC, CMC, CMC, IgE , 3pt IgE, 8pt Ion, 3pt XH NMR (CDC13): d 1.50 (s, N4- (2,2-Dimetü-3-6H), 2.25 (s, 3H), 2.93 (d, J = oxo-4H- 4.8 Hz, 3H), 4.57 (s, 2H), benz [1,4] oxazin-6-yl) -6.82 (m, 4H), 6.97 (t, J = 8.1 5-fluoro-N2- [2-methyl] - Hz, 1H), 7.19 (m, 2H), 7.40 1067 + 3- (N- (s, 1H), 7.54 (s, 1H), 7.81 (d, methylamino) carbonyl- J = 4.2 Hz, 1H); LCMS: methylenexyphenyl] -2.4- time ret .: 8.08 min; pyrythiamine purity: 99.78%; MS (m / e): 481.21 (MH Tí NMR (DMSO-d6): d 2.08 5-Fluoro-N2- [2-methyl- (s, 3H), 2.66 (d, J = 4.5 Hz, 3- (N - 3H), 4.46 (s, 2H), 4.58 (s, methylamin) carbonyl- 2H), 6.65 (dd, J = 1.8 and 7.2 1068 methyleneoxyphenyl) -N4- Hz, 1H), 7.04 (m, 2H), 7.15 (3-oxo-2H, 4H-5- (d, J = 8.7 Hz, 1H), 7.47 (d, pyrid [1,4] oxazin-6-yl) - J = 8.7 Hz, 1H), 7.84 (d , J = 2,4-pyrjmdindiamine 4.2 Hz, 1H), 8.01 (d, J = 3.6 Hz, 1H), 8.54 (s, 1H), 8.96 (T NMR (DMSO-d6): d 2.09 (s, 6H) , 4.62 (s, 2H), 7.05 (s, 2H), 7.28 (d, J = 8.4 Hz, 1H), N2- (3,5-Dimethyl-4- 7.55 (d, J = 8.1 Hz, 1H), 7.89 hydroxyethyl) -5-fluoro- (br, 1H), 8.07 (d, J = 3.6 Hz, 1069 N4- (3-oxo-2H, 4H-5-1H), 9.03 (s, 1H), 9.36 (s) ,? irid [1, 4] oxazin-6-yl) - 1H), 11.15 (s, 1H); 19F 2,4-pyrimidimediamine NMR (282 MHz, DMSO-d6): d-163.98; LCMS: time ret .: 7.9 TT NMR (CDC13): d 1.14 (t, N2- [3- (4- J = 7.2 Hz, 3H), 3.00 (t, J = Ethoxycarbonyl- 5.1 Hz, 4H), 3.46 ( t, J = 5.1 piperazine) phenyl] -5- Hz, 4H), 4.00 (q, J = 7.2 Hz, 1070 fluoro-N4- (3-oxo-2H), 4.47 (s, 2H), 6.55 (dd, + 2H, 4H-5- J = 1.8 and 8.4 Hz, 1H), 6.90? Irid [1, 4] oxazin-6-yl) - (dd, J = 1.2 and 7.8 Hz, 1H), 2,4-pyriridinediamine 6.98 (t, J = 2.1 Hz, 1H), 7.04 (d, J = 8.7 Hz, 1H), 7.08 T NMR (CDC13): d 2.01 (s, 3H), 3.02 (t, J = 5.1 Hz, 2H) , N2- [3- (4- 3.08 (t, J = 5.1 Hz, 2H), 3.50 Acetylpiperazin) phenyl] - (t, J = 5.1 Hz, 2H), 3.58 (t, J = 5-fluoro-N4- (3-oxo-1071 5.4 Hz, 2H), 4.50 (s, 2H), + 2H, 4H-5-6.66 (dd, J = 2.4 and 8.4 Hz, pyrid [1,4] oxazin-6-yl) - 1H), 6.87 (t, J = 2.4 Hz, 1H), 2,4-pyrimidiamine 6.92 (ddd, J = 0.9, 2.1 and 7.8 Hz, 1H), 6.98 (d, J No. Compound Name Physical Data Triptase Tftase Tftasa f syk Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt T NMR (DMSO-d6): d 1.20 N2- [4- (4- (t, J = 7.2 Hz, 3H), 2.99 (t, J = Etoxicarbo nil- 5.1 Hz, 4H), 3.49 (t, J = 5.1 piperazin) phenyl] -5- Hz, 4H), 4.05 (q, J = 7.2 Hz, 1072 fluoro-N4- (3-oxo- 2H), 4.63 (s, 2H), 6.83 (d, J = 2H, 4H-5-9.3 Hz, 2H), 7.36 (d, J = 8.4 pyrid [1, 4] oxazin-6-yl) - Hz, 1H), 7.47. (d, J = 9.0 Hz, 2,4-± ± nidindiamine 2H), 7.56 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 3.6 Hz, 1! H NMR (DMSO-d6): d 2.98 (t, J = 5.1 Hz, 4H), 3.69 (t, J = 5-Fluoro-N2- (3-1.1 Hz, 4H), 4.62 (s, 2H), morpholinophenyl) -N4- (3-6.50) (d, J = 7.2 Hz, 1H), 7.04 1073 oxo-2H, 4H-5- (t, J = 7.5 Hz, 1H), 7.17 (d, + pyrid [1,4] oxazin-6-yl) - J = 7.2 Hz, 1H), 7.18 (s, 1H), 2,4-pyrimidinediamine 7.33 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 8.11 (d, J = 3.6 Hz, 1H), 9.09 (s Ti NMR (DMSO-d6): d 2.85 (s, 3H), 2.90 (m, 2H), 3.23 5-Fluoro-N2- [3- (4- (m, 4H) , 3.67 (m, 2H), 4.63 methylpiperazine) phenyl] - (s, 2H), 6.57 (dd, J = 2.1 and 8.4 1074 N4- (3-oxo-2H, 4H-5 Hz, 1H), 7.08 ( t, J = 8.1 Hz, + pyridfl, 4] oxazin-6-yl) -1H), 7.20 (s, 1H), 7.28 (m, 2,4-pyrimdindiamine 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 3.3 Hz, 1H), 9.1 T NMR (DMSO-d6): d 1.19 N4- (2,2-Dimethyl-3- (t, J = 7.2 Hz, 3H), 1.42 (s, oxo-4H-5-6H), 3.00 (t, 4H), 3.45 (t, J = pyrid [1,4] oxazin-6-yl) - 4.8 Hz, 4H) , 4.04 (q, J = 7.2 1075 N2- [3- (4- Hz, 2H), 6.51 (d, J = 9.3 Hz, + ethoxycarbonylpiperazine) 1H), 7.03 (t, J = 8.1 Hz, 1H), phenyl ] -5-fluoro-2,4-7.18 (s, 1H), 7.20 (d, J = 6.6 pyrimidindiamine Hz, 1H), 7.34 (t, J = 8.4 Hz, 1H), 7.59 (d, J = 8.7 Hz Ti NMR (CDC13): d 1.46 (s, 6H), 2.06 (s, 3H), 3.08 (t, J = N2- [3- (4- 5.1 Hz, 2H), 3.13 (t, J = 5.1 Acetylpiperazin) phenyl] - Hz, 2H), 3.54 (t, J = 5.1 Hz, N4- (2,2-dimethyl-3-oxo- 1076 2H), 3.65 (t, J = 5.1 Hz, 2H), 4H-5- pyrid [1,4] oxazin- + 6.67 (dd, J = 2.4 and 8.4 Hz, 6-yl) -5-fluoro-2,4-1 H), 6.94 (t, J = 2.1 Hz, 1H), pyrinidinediamine 7.01 (ddd, J = 0.9, 1.8 and 7.8 Hz, 1H), 7.05 (d, J No. Compound Name Physical Data Triptase Triptase Tftasa f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE , 8pt Ion, 3pt XH NMR (DMSO-d6): d 1.20 N4- (2,2-Dimethyl-3- (t, J = 7.2 Hz, 3H), 1.43 (s, oxo-4H-5-? Irid 6H), 3.03 (t, 4H), 3.50 (t, [l , 4] oxazin-6-yl) -N2- 4H), 4.05 (q, J = 7.2 Hz, 2H), 1077 [4- (4-ethoxycarbonyl-6.88 (d, J = 9.3 Hz, 2H), 7.38 + piperazin) phenyl] -5- (d, J = 8.4 Hz, 1H), 7.45 (d, fluoro-2,4- J = 9.9 Hz, 2H), 7.51 (d, J = pijrirnidindiamine 8.7 Hz, 1H), 8.09 (d, J = 3.9 Hz, 1H), 9.24 (s, 1H), 9.44 T NMR (DMSO-d6): d 1.42 (s, 6H), 3.00 (t, J = 4.8 Hz, N4- (2.2 -Dimethyl-3-4H), 3.69 (t, J = 4.8 Hz, 4H), oxo-4H-5-6.51 (dd, J = 7.5 Hz, 1H), pyrid [1,4] oxazin-6-yl) - 1078 7.04 (t, J = 7.8 Hz, 1H), 7.16 + 5-fluoro-N2- (3- (s, 1H), 7.17 (d, J = 8.4 Hz, morpholinophenyl) -2.4- 1H), 7.34 (d, J = 8.4 Hz, 1H), pyrirnididiamine 7.59 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 3.6 Hz, 1H), 9.17 (XH NMR (DMSO-d6): d 1.39 N4 - (2,2-Dimethyl-3- (s, 6H), 2.08 (s, 3H), 2.65 (d, oxo-4H-5-pyrid J = 4.8 Hz, 3H), 4.45 (s, 2H), [ 1, 4] oxazin-6-yl) -5- 6.64 (dd, J = 2.7 and 6.6 Hz, 1079 fluoro-N2- [2-methyl-3-1H), 7.04 (, 2H), 7.15 (d, + (N-methyamin) - J = 8.4 Hz, 1H), 7.48 (d, J = carbonylmethylenexyphenyl 8.4 Hz, 1H), 7.84 (d, J = 3.9] -2, 4-p? Im lindiamine Hz, 1H), 8.01 (d, J = 3.6 Hz, 1H), 8.56 (s, 1H), 8.98 (* H NMR (CDC13): d 1.42 (s, 6H), 2.77 (s) , 3H), 3.20 (m, N4- (2,2-Dimetü-3-4H), 3.30 (m, 4H), 6.61 (d, oxo-4H-5-pyrid J = 6.9 Hz, 1H), 6.92 ( t, J = [1,4] oxazin-6-yl) -5- 2.4 Hz, 1H), 7.04 (d, J = 8.4 1080 + fluoro-N2- [3- (4- Hz, 1H), 7.13 ( m, 2H), 7.70 methylpiperazine) phenyl] - (d, J = 8.7 Hz, 1H), 7.81 (d, 2,4-pmmidindiamine J = 4.2 Hz, 1H); 19 F NMR (282 MHz, CDC13): d-162.81; LCMS XH NMR (DMSO-d6): d 1.45 (d, J = 6.6 Hz, 3H), 3.77 (s, (S) -N2- (3-Chloro-4- 3H), 4.73 (q, J = 6.6 Hz , 1H), methoxyphenyl) -5-fluoro-6.99 (d, J = 9.0 Hz, 1H), 7.38 N4- (2-methyl-3-oxo-1081 (d, J = 8.4 Hz, 1H), 7.48 (m , -t- + 2H, 4H-5- 2H), 7.80 (d, J = 2.1 Hz, 1H), pyrid [1,4] oxazin-6-yl) -8.11 (d, J = 3.6 Hz, 1H) , 9.21 2,4-? Irirm-mydiamine (s, 1H), 9.26 (s, 1H), 11.09 (s, 1H); 19F NMR (282 M No. Compound Name Physical Data Triptase Tftase Triptase f syk Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO-d6): d 1.45 (d, J = 6.9 Hz, 3H), 3.59 (s, (S) -5-Fluoro-N4- (2-3H), 3.65 (s, 6H), 4.72 (q, J = methyl-3-oxo- 2H, 4H-5-6.6 Hz, 1H), 7.02 (s, 2H),? Irid [1,4] oxazin-6-yl) - 7.32 (d, J = 8.7 Hz, 1H), 7.65 1082 N2- ( 3,4,5- (d, J = 8.4 Hz, 1H), 8.11 (d, + + trimethoxyphenyl) -2,4- J = 3.3 Hz, 1H), 9.10 (s, 1H), pyrimidinediamine 9.17 (s, 1H), 11.07 (s, 1H); 19F NMR (282 MHz, DMSO-d6 XH NMR (DMSO-d6): d 4.46 (s, 2H), 4.52 (s, 2H), 6.76 (d, N2, N4- Bis (3-oxo-J = 9.3 Hz, 1H), 6.86 (d, J = 2H, 4H-8.7 Hz, 1H), 7.18 (m, 2H), 1083 benz [1,4] oxazin-6-yl) - 7.23 (d, J = 2.4 Hz, 1H), 7.33 + + -fluoro-2,4- (dd, J = 2.4 and 8.7 Hz, 1H), pyrimidmdiamine 8.00 (d, J = 3.6 Hz, 1H), 8.94 (s, 1H), 9.29 (s, 1H), 10.58 ( s, 1H), 10.63 (s, 1H); 1 XH NMR (DMSO-d6): d 1.44 (d, J = 6.9 Hz, 3H), 2.17 (s, (S) -N2- (3.5-6H), 4.72 (q, J = 6.9 Hz, 1H ), Dimethylphenyl) -5-fluoro- 6.52 (s, 1H), 7.22 (s, 2H), N4- (2-methyl-3-oxo- 7.35 (d, J = 8.7 Hz, 1H), 7.89 1084 2H, 4H-5- (d, J = 8.4 Hz, 1H), 8.11 (d, + pyrid [1,4] oxazin-6-yl) - J = 3.6 Hz, 1H), 9.09 (s, 1H), 2, 4-pyrimidiamine 9.16 (s, 1H), 11.08 (s, 1H); 19F NMR (282 MHz, DMSO-d6 JH NMR (CDC13): d 1.82 (m, 2H), 2.03 (m, 2H), 2.15 (s, 3H), 2.46 (m, 2H), 3.20 N2- [3- (4- (m, 4H), 3.63 (t, J = 5.1 Hz, Acetylpiperazine) phenyl] -1085 2H), 3.78 (t, J = 5.1 Hz, 2H), N4-cyclobutyl-5-fluoro- + 4.58 ( m, J = 8.1 Hz, 1H), 5.26 2,4-pyrimidinediamine (d, J = 6.6 Hz, 1H), 6.58 (dd, J = 1.8 and 8.1 Hz, 1H), 7.01 (dd, J = 1.5 and 7.8 Hz, 1H), XH NMR (DMSO-d6): d 1.29 (s, 9H), 4.64 (s, 2H), 5.59 (s, N2- (5-tert-1H), 7.10 (d, 1H), 7.47 (d, J = Butylpyrazol-3-yl) -5- 6.6 Hz, 1H), 8.24 (d, 1H), fluoro-N4- (3-oxo-10.02 (s, 1H), 10.40 (s, IB); 1086 2H, 4H-5- 19F NMR (282 MHz, pyrid [1,4] oxazin-6-yl) -DMSO-d6): d-162.59; 2,4-? Irimidinediamine LCMS: ret time: 10.51 min; purity: 78.44%; MS (m / e): 399.24 (MH +).

No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (CDC13): d 1.78- 1.87 (m, 2H), 1.96-2.03 (m, 2H), 2.32 (s, 6H), 2.44-2.53 (m, 2H), 4.56 (m, J = 7.8 Hz, N4-Cyclobutyl-N2- (3.5-1H) , 5.26 (d, J = 7.8 Hz, 1H), 1087 dimetüfeml) -5-fluoro- + 6.67 (s, 1H), 7.23 (s, 2H), + 2,4-pyrimid diamine 7.34 (br, NH, 1H ), 7.72 (d, J = 2.7 Hz, 1H); 19 F NMR (282 MHz, CDC13): d-168.35; LCMS: 1H NMR (CDC13): d 1.71-1.86 (m, TH), 1.93-2.06 (m, 2H), 2.43-2.53 (m, 2H), 3.81 N4-Cyclobutyl-N2- (3.5- (s) , 6H), 4.60 (m, J = 7.8 Hz, dimethoxyphenyl) -5- 1H), 5.31 (d, 1H), 6.16 (t, J = 1088 fluoro-2.4- 2.1 Hz, 1H), 6.84 (d , J = 2.1 pirintidindiamine Hz, 2H), 7.57 (br, NH, 1H), 7.72 (d, J = 3.6 Hz, VH); 19 F NMR (282 MHz, CDC13): d-167 1 H NMR (CDC13): d 1.75-2.04 (m, 4H), 2.43-2.53 (m, 2H), 3.85 (s, 3H), 4.58 (m, N4- Cyclobutyl-5- J = 7.8 Hz, 1H), 5.32 (d, J = fluoro-N2- (3-methoxy- 6.6 Hz, 1H), 6.76 (s, 1H), 1089 5-trifluoromethylphenyl) - + 7.18 (t , J = 2.1 Hz, 1H), 7.52 + 2,4-? Irimidindiamine (br, NH, 1H), 7.76 (s, 2H); 19 F NMR (282 MHz, CDC13): d-167.20, -63.67; LCMS: Ret. Time: N4- (5-tert-Butyl-1H-LCMS: ret. Time: 11.58 pyrazol-3-yl) -5-fluoro-1090 min; purity: 90.45%; MS + N2- (3-morpholinophenyl) - + (m / e): 412.33 (MH +). 2,4-? Irimidindiamine 1H NMR (CDC13): d 1.20 (s, 9H), 2.04 (s, 3H), 3.06 (t, J = 5.4 Hz, 2H), 3.11 (t, J = 5.1 N2- [3 - (4- Hz, 2H), 3.53 (t, J = 5.1 Hz, Acetyl? I? Erazin) phenyl] - 2H), 3.63 (t, J = 5.1 Hz, 2H), 1091 N4- (5-tert. butyl-lH- 6.10 (s, 1H), 6.57 (m, 1H), + pyrazol-3-yl) -5-fluoro-6.96 (s, 1H), 7.13 (m, 2H), 2,4-? irintidindiamine 7.82 (d, J = 3.9 Hz, 1H); LCMS: ret time: 8.84 min; No. Name of Compound Physical Data Triptase Tftase Triptase f sik Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.30 (s, 9H) , 1.47 (d, J = 6.6 (S) -N2- (5-tert-Butyl-Hz, 3H), 4.74 (q, J = 6.3 Hz, lH-pyrazol-3-yl) -5- 1H), 5.60 (s, 1H), 7.09 (d, J = fluoro-N4- (2-methyl-3-9.0 Hz, 1H), 7.49 (d, J = 8.4 1092 oxo-2H, 4H-5 Hz, 1H), 8.23 (d, J = 3.9 Hz, + 1 H NMR (DMSO-d 6): d 2.16 (s, 6 H), 3.61 (s, 4 H), 3.64 (s, 3 H), 6.98 (d, J = 11 N 2 - (3,5-Dimethyl-4 Hz, 1H), 7.00 (s, 1H), 7.23 methoxyphenyl) -5-fluoro- (s, 1H), 7.35 (t, J = 8.1 Hz, 1093 [3- (N-2-imidazolin-2- 1H), 7.75 (d, J = 6.6 Hz, 1H), + + il) aminophenyl] -2.4- 8.19 (d, J = 4.5 Hz, 1H), 8.29 pirinud diamine (s, 2H), 9.57 (s, 1H), 9.89 (s, 1H), 10.82 (s, 1H); 19 F NMR (1 H NMR (DMSO-d 6): d 3.63 (s, 4 H), 3.79 (s, 3 H), 6.96 (d, J = 9.3 Hz, 1 H), 7.04 5-Fluoro-N 2 - (3-fluoro- (t, J = 9.3 Hz, 1H), 7.28 (m, 4-methoxyphenyl) -N4- [3-1H), 7.36 (t, J = 8.1 Hz, 1H), 1094 (N-2-imidazolin-2- 7.63 (dd, J = 2.1, 13.8 Hz, Ü) aminophenyl] -2.4- 1H), 7.68 (d, J = 9.6 Hz, 1H), pyr? M ^ mdiamine 7.80 (s, 1H), 8.18 (d) , J = 4.2 Hz, 1H), 8.27 (s, 1H), 9.56 (s, 1H NMR (DMSO-d6): d 2.20 (s, 6H), 3.60 (s, 4H), 6.92 (s, 1H), 6.98 (, 1H), N2- (3,5-Dimethylphenyl) - 7.22 (s, 1H), 7.35 (t, J = 8.1 5-fluoro-N4- [3- (N-2- Hz, 1H), 7.73 (d, J = 7.8 Hz, 1095 imidazoline-2- 1H), 7.80 (s, 1H), 8.21 (d, J = ü) aminophenyl] -2.4- 4.2 Hz, 1H), 8.26 (s, 2H) , pyridinediamine 9.60 (s, 1H), 9.86 (s, 1H), 10.80 (s, 1H); 19 F NMR (282 MHz, D 1 H NMR (DMSO-d 6): d 3.62 (s, 4 H), 3.66 (s, 6 H), N 2 - (3.5 - 6.13 (t, J = 2.1 Hz, 1 H), 6.92 Dimethoxyphenyl) -5- (d, J = 2.1 Hz, 1H), 6.95 (dd, fluoro-N4- [3- (N-2-1096 J = 1.5, 8.4 Hz, 1H), 7.34 (t, imidazolin-2) - J = 8.4 Hz, 1H), 7.71 (d, J = ü) aminophenyl] -2.4- 8.1 Hz, 1H), 7.93 (s, 1H), pyrimidinediamine 8.20 (d, J = 3.9 Hz, 1H), 8.26 (s, 2H), 9.61 (s, lH), 9.81 (s, No. Name of Compound Physical Data Triptase Tftase Triptase f sik Com ID, ID, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1 H NMR (DMSO-d 6): d 3.01 (t, J = 4.5 Hz, 4H), 3.60 5-Fluoro-N 4 - [3- (N-2- (s, 4H), 3.70 (t, J = 4.5 Hz, imidazolin-2- 4H), 6.51 (dd, J = 2.1.8.4 Hz, 1097 il) aminofeml] -N2- (3-1H), 6.90 (dd, J = 1.5, 7.8 Hz, morpholinophenyl) - 2.4-1H), 7.05 (t, J = 8.1 Hz, 1H), pyrimidinediamine 7.29 (m, 3H), 7.64 (d, J = 7.8 Hz, 1H), 8.01 (s, 1H), 8.12 (d, J = 3.6 Hz, 1H), 9.20 (1 H NMR (DMSO-d6): d 1.20 (t, J = 7.2 Hz, 3H), 3.02 N2- [3- (4- (t, J = 5.4 Hz, 4H) , 3.47 (t, J = Ethoxycarbonyl- 5.4 Hz, 4H), 3.60 (s, 4H), piperazine) -phenyl] -5- 4.05 (q, J = 7.2 Hz, 2H), 6.53 1098 fluoro-N4- [3- (N-2- (dd, J = 1.5, 8.4 Hz, 1H), 6.90 imidazolin-2- (d, J = 8.1 Hz, 1H), 7.06 (t, ü) aminophenyl] -2.4- J = 8.1 Hz, 1H), 7.30 (m, pyrimid diamine 3H), 7.66 (d, J = 8.7 Hz, 1H), 7 1 H NMR (DMSO-d6): d 3.30 (m, 4H), 3.62 (s, 4H), 5-Fluoro-N4- [3- (N-2- 6.84 (d, J = 9.0 Hz, 2H), 6.91 imidazolia-2- (d, J = 8.1 Hz, 1H), 7.35 (t, il) aminophenyl] -N2- [4- J = 8.1 Hz, IB), 7.49 (d, J = 1099 (4-methylpiperazine) - 8.4 Hz, 2H), 7.73 (d, J = 8.4 phenyl] -2.4-Hz, 1H), 7.80 (s, 1H), 8.09 pyrimidine diamine (d, J = 3.3 Hz, 1H), 8.27 (s, 1H), 9.06 (s, 1H), 9.44 (s, 1H), 1 1H NMR (DMSO-d6): d 3.00 (t, J = 5.1 Hz, 4H), 3.50 5-Fluoro-N4- [3- (N-2- (t, J = 4.5 Hz, 4H), 3.61 (s, imidazolin-2-7H), 6.84 (d, J = 9.0 Hz, 2H), il) aminophenyl] -N2- [4- 1100 6.91 (dd, J = 1.5, 7.5 Hz, 1H), (4-methoxycarbonyl- 7.34 (t, J = 7.8 Hz, 1H), 7.52 piperazine) -fenu] -2.4- (d, J = 8.7 Hz, 2H), 7.66 (d, pyrimidindiamine J = 8.1 Hz, 1H), 7.94 ( s, 1H), 8.08 (d, J = 3.6 Hz, 1H), 9 1H NMR (CDC13): d 1.28 (t, J = 7.2 Hz, 3H), 1.31 (s, 9H), N4- (5-tert. -Butil-lH- 3.13 (t, J = 5.1 Hz, 4H), 3.60 pyrazol-3-yl) -N2- [3- (4- (t, J = 5.4 Hz, 4H), 4.15 (q, 1101 ethoxycarbonylpiperazin ) J = 7.2 Hz, 2H), 6.35 (s, 1H), + -fenu] -5-fluoro-2,4-6.61 (m, 1H), 7.03 (s, 1H), pydimidiamine 7.18 (m, 2H) , 7.73 (br, 1H), 7.90 (d, J = 3.3 Hz, 1H), 8.20 (br, 1H); 19FRMN (282 No. Compound Name Physical Data Triptase Tftase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- [4- (4-Acetylpiperazin) phenyl] -MSCM: Ret Time: 8.02 1102 N4- (5-tert-butyl-1H-min; purity: 94.49%; MS + pyrazol-3-yl) -5-fluoro- (m / e): 453.29 (MH +). 2,4-pyridine N 4 - (5-tert-Butyl-1H-pyrazol-3-yl) -5-fluoro-N 2 - [4- (4-CLEM: retentate time: 10.38-1103 min, purity: 97.48%; MS methoxycarbonyl- + + (m / e): 469.35 (MH +).? I? Erazin) phenyl] -2,4- pyrimidinediamine 1H NMR (DEMO-d6): d 1.26 (s, 9H), 2.61 (m, 7H), 3.00 (m, 4H), 6.30 (br, 1H), N4- (5-tert-Butyl-lH-6.86 (d, J = 8.4 Hz, 2H), 7.48 pyrazole-3-yl) -5- fluoro- (d, J = 9.3 Hz, 2H), 7.97 (s, 1104 N2- [4- (4-1H); 19F NMR (282 MHz, + + methylpiperazine) phenyl] - DEMO-d6): d - 165.34; 2,4-pyrimidinediamine LCMS: time ret .: 6.04 min; purity: 90.75%; MS (m / e): 425 (MH +). 1 H NMR (DEMO-d 6): d 2.04 (s, 3 H), 2.97 (t, J = 4.8 N 2 - [4- (4 Hz, 2 H), 3.04 (t, J = 4.8 Hz, Acetylpiperazine) phenyl] - 2H), 3.57 (m, 4H), 3.61 (s, 5-fluoro-N4- [3- (N-2-4H), 6.84 (d, J = 9.0 Hz, 2H), 1105 imidazolin-2- 6.90 ( d, J = 9.3 Hz, 1H), 7.33 ü) aminophenyl] -2.4- (t, J = 7.8 Hz, 1H), 7.50 (d, pyrimidindiamine J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 1H), 7.79 (s, 1H), 8.08 N2- [3- (4-Acetyl-iperazine) phenyl] -MSCM: Ret. Time: 7.31 5-fluoro-N4- [3- (N-2- 1106 min., Purity: 84.11%; imidazolin-2- EM (m / e): 490.34 (MH +). Il) aminophenyl] -2,4-piirimidinediamine 1 H NMR (CDC13): d 1.42 (t, J = 7.2 Hz , 3H), 1.63-2.06 (m, 4H), 2.27-2.36 (m, 2H), N4-Cyclobutyl-N2- [2-4.41 (q, J = 7.2 Hz, 2H), 5.17 (ethoxycarbonyl) indole-7 - 1107 (d, J = 6.0 Hz, 1H), 7.06 (t, il] -5-fiuoro ~ 2.4- + J = 7.8 Hz, 1H), 7.14 (d, 1H), pyriadinedonylamine 7.22 (m, 2H), 7.28 ( br, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 3.6 Hz, lH), 10.68 No. Compound Name Physical Data Triptase Triptase Triptase f_sik Com ID, ID, ID, llpt CMC , CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (CDCB): d 1.73-2.05 (m, 4H), 2.40-2.50 (m, TH), 3.20 (t, J = 4.8 Hz, 4H) , 3.88 (1, N4-Cyclobutyl-5- J = 4.8 Hz, 4H), 4.60 (m, J = 7.8 fluoro-N2- (3-110 Hz, 1H), 5.14 (d, J = 6.3 Hz, morpholinophenyl) -2.4- + + 1H), 6.57 (dd, J = 2.4, 8.1 Hz, pyrimidinediamine 1H), 6.97 (dd, J = 1.8, 7.5 Hz, 1H), 7.06 (br, NH, 1H), 7.19 ( t, J = 8.1 Hz 1 H NMR (CDCB): d 1.29 (t, J = 6.9 Hz, 3H), 1.71-2.02 (m, 4H), N4-Cyclobutyl-N2- [3- 2.41-2.51 (, 2H) , 3.18 (t, J = (4- 5.1 Hz, 4H), 3.64 (t, J = 5.1 Hz, 1109 ethoxycarbonylpiperazin) + 4H), 4.17 (q, J = 6.9 Hz, 2H), feni] -5-fluoro -2.4- 4.59 (m, J = 8.1 Hz, 1H), 5.16 (d, pyrimid diamine J = 7.8 Hz, 1H), 6.58 (dd, J = 2.4, 8.1 Hz , lH), 6.97 (dd, J = 1.8, 1 H NMR (CDCB): d 1.65-1.74 (m, 2H), 1.85-1.95 (m, 2H), 2.19-2.33 (m, TH), 2.71 (s, 3H), N4-Cyclobutyl-5- 3.15 (t, 4IÍ), 3.32 (t, J = 4.8 Hz, fluoro-N2- [4- (4-1110 4H), 4.36 (m, J = 8.1 Hz, 1H) , + methylpiperazine) phenyl] - 6.80 (d, J = 9.0 Hz, 2H), 7.36 (d, 2,4-pyrimidinediamine J = 9.3 Hz, 2H), 7.55 (d, J = 4.2 Hz, 1H); 19 F NMR (282 MHz, CDCB): d 1 H NMR (CDCB): d 1.31 (t, 3H), 1.50-2.04 (m, 4H), 2.41- N 4 -cyclobutyl-N 2 - [4- 2.50 (, 2H), 3.08 (t, J = 4.8 Hz, (4-4H), 3.64 (t, J = 5.1 Hz, 4H), 1111 ethoxycarbomlpiperazin) 4.17 (q, 2H), 4.52 (m, J = 7.8 Hz, + phenyl) - 5-fluoro-2,4- 1H), 5.18 (d, J = 6.6 Hz, 1H), pyrir dindiamine 6.90 (d, J = 9.0 Hz, TH), 7.07 (br, 1H), 7.45 (d, J = 9.0 Hz, 2H), 7.70 (N2- [3- (4-Acetyl-iperazine) phenyl] -MSCM: ret time: 9.04 min;; 1112 N4- (3-cyclo? Ropil-lH- purity: 87.21%; (m / e): + + + pyrazol-5-yl) -5-fluoro-437.32 (MH +). 2,4-pyrididinediamine 1 H NMR (CDCB): d 0.54-0.64 (m, TH), 0.76- 0.86 (m, TH), N4- (3-Cyclopropyl-lH-VIA (m, VH), TAT (s, 3H), 2.76 pyrazol-5-yl) -5-fluoro- (br, 4H), 3.17 ( t, J = 4.8 Hz, 4H), 1113 N2- [4- (4-5.90 (br, 1H), 6.82 (d, J = 8.7 Hz, + methyl? iperazin) phenyl] -2H), 7.29 (d, J = 8.7 Hz, 2H), 167.69; LCM No. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3 pt N4- (3-Cyclopropyl-1H-CLEM: ret time: 8.57 pyrazol-5-yl) -5-fluoro-1114 min; purity: 88.76%; MS + N2- (3-morpholinophen) - + (m / e): 396.24 (MH +). 2,4-pyrimidindiamine 1H NMR (DMSO-d6): d 0.67 (m, 2H), 0.88 (m, 2H), 1.19 (t, J = 7.1 Hz, 3H), 1.85 N4- (3-Cycle? ropil-lH- (m, 1H), 3.06 (m, 4H), 3.48 pyrazol-5-yl) -N2- [3- (4- (m, 4H), 4.05 (q, J = 7.1 Hz, 1115 ethoxycarbonylpiperazine ) + 2H), 6.52 (d, J = 8.1 Hz, 1H), + phenyl] -5-fluoro-2,4-7.07 (m, 1H), 7.20 (m, 2H); pirinñdmdianiina CLEM: time ret: 11.80 min; purity: 79.43%; MS (m / e): 467.30 1 H NMR (DMSO-d 6): d 0.62 (m, 2H), 0.90 (m, TH), 1.20 (t, J = 7.2 Hz, 3H), 1.84 N4- (3-Cycle ? ropil-lH- (m, J = 3.9 Hz, 1H), 3.08 (br, pyrazole-5-ü) -N2- [4- (4-4H), 3.44 (br, 4H), 4.05 (q, 1116 ethoxycarbonylpiperazine) J = 6.9 Hz, 2H), 6.12 (br, + + phenyl] -5-fluoro-2,4- 1H), 6.93 (d, J = 8.7 Hz, 2H), pyrin? dindiamine 7.40 (d, J = 8.4 Hz, TH), 8.02 (d, J = 4.2 Hz, 1H), 9.37 (br, 1H 1H NMR (DMSO-d6): d 3.40 (t, J = 4.5 Hz, 2H), 4.10 (t, J = 4.5 Hz, 2H), 6.92 (d, 2-Chloro-5-fluoro-N4- J = 8.4 Hz, 1H), 7.04 (d, J = (3,4-dihydro-2H, 4H-5- 8.1 Hz , 1H), 8.27 (d, J = 3.6 1117 pyrid [1,4] oxazin-6-yl) - Hz, 1H), 9.80 (br, 1H); 19F 4-pyrirmd amine NMR (282 MHz, DMSO- d6 ): d-152.34; LCMS: ret time: 9.69 min, purity: 93.93%; MS (m / e): 2 1 H NMR (CDCB): d 1.45 (s, 9H), 3.18 (t, J = 4.8 Hz, 4H), 3.89 (m, 4H), 3.96 (m, 2H), N4- (l-terc- 4.28 (m, TH), 4.69 (m, 1H), Butoxycarbonyl azetidine 6.93 (d, J = 9.0 Hz, 2H), 7.36 1118 -3-yl) -5-fluoro-N2- (4- + (d, J = 9.3 Hz, 2H), 7.66. (d, morpholinophenyl) -2.4- J = 3.6 Hz, 1H); 19F NMR p-inidindianiin (282 MHz, CDCB): d-163.92; LCMS: ret time: 9.28 min; p No. Name of Compound Physical Data Tftase Triptase Tftasa f sik Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (CDCB): d 1.46 (s, 9H), 2.16 (s, 3H), 3.15 (p, J = N2- [4- (4- 5.1 Hz, 4H), 3.64 (t, J = 5.1 Acetylpiperazine) phenyl] - Hz, 2H), 3.78 (t, J = 5.1 Hz, N4- (l-tert-1119 2H), 3.91 (dd, J = 5.4, 9.9 Hz, butoxycarbonylazetidin-2H), 4.30 (dd, J = 7.8, 9.6 Hz, 3-yl) -5-fluoro- 2.4-2H), 4.70 (m, 1H), 6.91 (d, pyrimidinediamine J = 9.3 Hz, 2H), 7.38 (d, J = 9.3 Hz, TH), 7.72 (d, 1H NMR (CDCB): d 1.45 (s, 9H), 2.16 (s, 3H), 3.21 (m, N2- [3- (4-4H), 3.64 (m, TH), 3.78 (m, Acetylpiperazin) phenyl] -2H), 3.99 ( dd, J = 4.8, 9.0 Hz, N4- (l-tert-1120 2H), 4.30 (dd, J = 7.8, 9.3 Hz, butoxycarbonylazetidin-2H), 4.74 (m, 1H), 6.75 (d, 3-il ) -5-fluoro-2,4- J = 5.1 Hz, 1H), 6.90 (d, J = pyrimidinediamine 8.7 Hz, 1H), 7.19 (m, 1H), 7.26 (m, 1H), 7.69 (d, J) = 4 N4- (3-Cyclopropyl-1H-CLEM: ret time: 7.80 pyrazol-5-yl) -5-fluoro-1121 min, purity: 96.17%; N2- EM (4-mo) rfolinphenyl) - + (m / e): 396.22 (MH +). 2,4-p-imidindiamine N4- (l-tert-Butoxycarbonyl azetidine LCMS: retentate time: 10.44 -3-yl) -N2- [4- (4-1122 min, purity: 82.19%, ethoxycarbonylpiperazi MS (m / e): 516.26 (MH +). n) phenyl] -5-fluoro-2,4-pyrinidinediamine N4- (Azetidin-3-yl) -5-CLEM: ret time: 2.12 fluoro-N2- (4-1123 min. Purity: 88.18%; MS morpholinophenyl) -2.4- (m / e): 345.21 (MH +). pyrimidinediamine N2- [4- (4-acetylpiperazine) femyl] -MSC: time ret: 2.33 1124 N4- (azetidin-3-yl) -5- min; purity: 92.29%; EM fluoro-2,4- (m / e): 386.25 (MH +). pyrimid dia ina N4- (Azetidin-3-yl) -N2- [4- (4- CLEM: time ret .: 7.44 1125 ethoxycarbonylpiperazin) min; purity: 85.69%; Phenyl] -5-fluoro-2,4- (m / e): 416 (MH +). pyrimidinediamine N4- (Azetidin-3-yl) -5-CLEM: ret time: 2.85 fluoro-N2- (3-1126 min, purity: 100%, morpholinophenyl MS) -2.4- + (m / e) : 345.24 (MH +). pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f_sik Com ID, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- [3- (4-Acetylpiperazin) phenyl] - CLEM: time ret: 3.10 1127 N4- (azetidin-3-yl) -5- min; purity: 88.30%; MS + fluoro-2,4- (m / e): 386.28 (MH +). pyrimidiamine 1 H NMR (DMSO-d 6): d 3.00 (t, J = 4.8 Hz, 4H), 3.38 N4- (3,4-Dihydro- (t, 2H), 3.72 (t, J = 4.8 Hz, 2H, 4H -5- 4H), 4.08 (t, J = 4.2 Hz, 2H), pyridine 1, 4] oxazin-6-yl) - 1128 6.50 (br, 1H), 6.82 (d, J = 9.0 5-fluoro-N2) - (4- Hz, 2H), 6.93 (d, J = 8.1 Hz, morpholinophenyl) -2.4- 1H), 7.20 (d, J = 8.1 Hz, 1H), pyrimidinediamine 7.48 (d, J = 9.3 Hz, 2H), 7.99 (d, J = 3.6 Hz, 1H), 8.65 (N4- (l-tert-Butoxycarbonylazetidine CLEM: ret time: 11.35 -3-yl) -N2- [3- (4-1129 min, purity : 86.05%; EM-ethoxycarbonylpiperazine) (m / e): 516.32 (MH +). Phenyl] -5-fluoro-2,4-puimidindiamine N4- (Azetidin-3-yl) -N2- [3- (4- CLEM: time ret: 8.39 1130 ethoxycarbonnapiperazine) min, purity: 96.94%, Phenyl MS-5-fluoro-2,4- (m / e): 416 (MH +), pyrimidinediamine N4- (Azetidin-3-yl) -5 - LCMS: time ret .: 1.20 fluoro-N2- [4- (4-1131 min, purity: 96.44%, EM methyl-i erazin) phenyl] - (m / e): 358.24 (MH +) .2, 4-pminidindiamine 1H NMR (DMSO-d6): d 3.38 (t, 2H), 4.08 (t, J = 4.5 N4- (3,4-Dihydro-Hz, 2H), 6.52 (br , 1H), 6.78 2H, 4H-5- (d, J = 8.1 Hz, 1H), 7.27 (m, pyrid [1,4] oxazin-6-yl) -3H), 7.50 (s, 1H), 7.67. (d, J = 1132 5-fluoro-N2- [3-1.1 Hz, 1H), 8.01 (s, 1H), + (oxazol-5-yl) phene] -2.4- 8.08 (d, J = 3.6 Hz, 1H), 8.38 pyrrmidindiamine (s, 1H), 8.82 (s, 1H), 9.35 (s, 1H); 19 F NMR (282 MHz, 1 H NMR DMSO (CDCB): d 1.68-1.76 (m, 2H), 2.17-2.25 (m, 4H), 3.14 (d, J = 3.0 Hz, 3H), 2-Chloro-N4- cyclobutyl- 4.79 (m, J = 8.4 Hz, 1H), 7.85 1133 5-fluoro-N4-methyl-4- (d, J = 6.0 Hz, 1H); 19F pirintidmamine NMR (282 MHz, CDCB): d - 150.50 LCMS: ret time: 13.83 min, purity: 96.47%, MS (m / e): 216.10 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d N2- [4- ( 4- 2.03 (s, 3H), 2.97 (t, J = 5.1 Acetylpiperazin) phenyl] - Hz, 2H), 3.03 (t, J = 5.1 Hz, N4- (3,4-dihydro-2H), 3.39 (t, 2H), 3.56 (t, 1134 2H, 4H-5-4H), 4.08 (t, J = 4.2 Hz, 2H), + pyrid [1,4] oxazin-6-yl) - 6.51 (s, 1H), 6.84 (d, J = 9.0 5-fluoro-2,4-Hz, 2H), 6.93 (d, J = 8.4 Hz, pyrjm? D diamine 1H), 7.19 (d, J = 8.1 Hz, 1H) , 7.49 (d, J = 9.0 Hz, 2H), 7.99 1 H NMR (DMSO-d6): d 1.19 (t, J = 7.2 Hz, 3H), 2.99 N4- (3,4-Dihydro- (t, J = 5.4 Hz, 4H), 3.39 (t, 2H, 4H-5- TH), 3.49 (t, 4H), 4.04 (q, J = pyridfl, 4] oxazin-6-yl) - 7.2 Hz, TH), 4.08 (t, J = 4.8 1135 N2- [4- (4- Hz, 2H), 6.51 (s, 1H), 6.84 + + ethoxycarbonylpiperazine) (d, J = 9.3 Hz, 2H), 6.93 (d, phenyl) - 5-fluoro-2,4- J = 8.4 Hz, 1H), 7.19 (d, J = pyridine diamine 8.4 Hz, 1H), 7.49 (d, J = 9.0 Hz 1H NMR (DMSO-d6): d 2.99 (t , J = 5.1 Hz, 4H), 3.39 N4- (3,4-Dihydro- (t, 2 H), 3.69 (t, J = 4.8 Hz, 2H.4H-5-4H), 4.08 (t, J = 4.2 Hz, TH), pyrid [1,4] oxazin-6-yl) - 6.50 (, 2H ), 6.91 (d, J = 8.4 1136 5-fluoro-N2- (3 Hz, 1H), 7.04 (t, J = 8.1 Hz, + + morpholinophenyl) -2.4- 1H), 7.19 (m, 3H ), 8.04 (d, pyrimidinediamine J = 3.6 Hz, 1H), 8.74 (s, 1H), 9.02 (s, 1H); 19 F NMR (282 MH 1 H NMR (DMSO-d 6): d 2.03 (s, 3 H), 2.98 (t, J = 4.8 N 2 - [3- (4 Hz, 2 H), 3.05 (t, J = 4.8 Hz, Acetylpiperazin) phenyl] -2H), 3.39 (t, 2H), 3.53 (t, J = N4- (3,4-dihydro- 5.4 Hz, 4H), 4.08 (t, 2H), 1137 2H, 4H- 5- 6.50 (m, 2H), 6.91 (d, J = 8.4 + + pyrid [1,4] oxazin-6-yl) - Hz, 1H), 7.04 (t, J = 8.4 Hz, 5-fluoro-2) , 4-1H), 7.21 (m, 3H), 8.04 (d, J = 3.6 Hz, 1H), 8.75 (s, 1H), 9 1H NMR (DMSO-d6): d N4- (3,4-Dihydro - 1.20 (t, J = 7.2 Hz, 3H), 3.01 2H, 4H-5- (t, J = 4.8 Hz, 4H), 3.41 (t, pyrid [1, 4] oxazin-6-yl) - 2H) , 3.46 (t, J = 4.8 Hz, 4H), 1138 N2- [3- (4- 4.08 (t, 2H), 6.50 (m, 2H), + ethoxycarbonylpiperazin) 6.91 (d, J = 8.4 Hz, 1H) , 7.04 phenyl] -5-fluoro-2,4- (t, J = 8.4 Hz, 1H), 7.19 (d, pmmidmdiamine J = 8.1 Hz, 2H), 7.25 (t, 1H), 8.04 (d, J = 3.6 Hz, 1H), 8.73 No. Compound Name Physical Data Tftase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6 ): d 1.56-1.69 (m, 2H), 2.07-2.27 (m, 4H), 3.07 (t, J = 4.5 Hz, N4-Cyclobutyl-5-4H), 3.12 (d, J = 3.0 Hz, 3H), fluoro-N4-methyl-N2-3.73 (t, J = 4.5 Hz, 4H), 4.76 1139 (4-morpholinophenyl) -2.4- (, J = 8.4 Hz, 1H), 6.92 (d, pyrimidinediamine J = 9.0 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 7.2 Hz, 1H ), 9.36 (br, 1H); 19F NMR 1H NMR (DMSO-d6): d 1.59-1.69 (m, 2H), 2.03 (s, 3H), 2.10-2.27 (m, 4H), 3.03 N2- [4- (4- (t, J = 4.5 Hz, 2H), 3.11 (d, Acetylpiperazine) phenyl] - J = 3.0 Hz, 5H), 3.56 (t, 4H), 1140 N4-cyclobutyl-5-fluoro- 4.76 (m, J = 7.5 Hz, 1H) , 6.93 + N4-methyl-2,4- (d, J = 9.0 Hz, 2H), 7.45 (d, pijrimidindiamine J = 9.0 Hz, 2H), 7.96 (d, J = 7.2 Hz, 1H), 9.26 (br , 1 HOUR); LCMS 1 H NMR (DMSO-d 6): d 2.23 (s, 3 H), 3.03 (t, 4 H), N 4 - (3,4-Dihydro-3.29 (m 4 H), 3.38 (t, 2 H), 2 H, 4 H- 5- 4.08 (t, J = 4.5 Hz, 2H), 6.50 pyrid [1, 4] oxazin-6-yl) - (br, 1H), 6.81 (d, J = 8.7 Hz, 1141 + 5-fluoro-N2 - [4- (4- 2H), 6.92 (d, J = 8.4 Hz, 1H), methylpiperazine) phenyl] - 7.20 (d, J = 8.1 Hz, 1H), 7.46 2,4-pyrmidinediamine (d, J = 9.0 Hz, 2H), 7.98 (d, J = 3.6 Hz, 1H), 8.64 (br, 1H), 1H NMR (DMSO-d6): d 2.20 (s, 3H), 2.41 (t, 4H), N4- (3,4-Dihydro-3.03 (t, 4H), 3.38 (t, 2H), 2H, 4H-5- 4.08 (t, J = 4.8 Hz, 2H), 6.50 pyrid [1, 4] oxazin-6 il) - (m, 2H), 6.91 (d, J = 7.8 Hz, 1142 5-fluoro-N2- [3- (4-1H), 7.02 (t, J = 7.8 Hz, 1H), + + methylpiperazine) phenyl] - 7.20 (m, 3H), 8.03 (d, J = 3.6 2,4-? matid diamine Hz, 1H), 8.72 (s, 1H), 8.99 (s, 1H); 19 F NMR (282 MHz, DMSO-1 H NMR (DMSO-d 6): d 3.53 (t, J = 4.2 Hz, TH), 4.16 N 4 - (3,4-Dihydro- (t, J = 4.2 Hz, 2H), 6.84 (d, 2H, 4H-5- J = 8.7 Hz, 1H), 7.24 (d, J =? Irid [1,4] oxazin-6-yl) -1143 8.7 Hz, 1H), 7.35 (s, 1H) ), + 5-fluoro-N2- [3- 7.40 (t, J = 7.8 Hz, 1H), 7.56 (oxazol-2-yl) phenyl] -2,4- (dt, J = 1.2, 8.1 Hz, 1H ), 7.89 piri idindiamine (d, J = 8.4 Hz, 1H), 8.18 (s, 1H), 8.32 (d, J = 3.3 Hz, lH), 8 No. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID , ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 0.61-0.66 (m, 2H), 0.86 (m, 2H), 1.81 (m, 1H), 6.41 (br, N4- (3-Cyclopropyl-1H-1H), 7.35 (, 2H), 7.52 (d, pyrazol-5-yl) -5-fluoro-J = 7.5 Hz, 1H), 7.86 ( s, 1H), 1144 N2- [3- (oxazole-2- + 8.04 (s, 1H), 8.19 (m, 2H), + il) phenyl] -2.4- 9.34 (s, 1H), 9.60 ( s, 1H); pyrinindianamine 19 F NMR (282 MHz, DMSO-d 6): d-163.42; LCMS: ret time: 9.50 mL 1 H NMR (DMSO-d 6): d 3.49 (t, 2 H), 3.61 (s, 3 H), N 4 - (3,4-Dihydro-3.69 (s, 6 H), 4.14 (t, J = 4.5 2H, 4H-5 Hz, 2H), 6.94 (d, J = 7.8 Hz, pyrid [1,4] oxazin-6-yl) -1H), 7.07 (s, 2H), 7.14 (d, 1145 + 5-fluoro-N2- (3.4.5- + 1H), 8.20 (d, J = 3.6 Hz, 1H), trimethoxyphenyl) -2.4-9.75 (s, 1H); LCMS: pyrimimidhamine time ret: 8.80 min; purity: 100%; MS (m / e): 429.45 (MH +). 1 H NMR (DMSO-d 6): d 3.39 (s, 2 H), 3.78 (s, 3 H), N 2 - (3-Chloro-4- 4.08 (t, J = 3.9 Hz, 2 H), 6.54 methoxyphenyl) -N 4- (3, 4- (br, 1H), 6.95 (d, J = 8.4 Hz, dihydro-2H, 4H-5-1146 1H), 7.00 (d, J = 8.7 Hz, 1H), + pyrid [l, 4 ] oxazin-6-yl) - 7.13 (d, J = 8.4 Hz, 1H), 7.46 5-fluoro-2,4- (dd, J = 2.4, 9.0 Hz, 1H), 7.84 pyrimidinediamine (d, J = 2.4 Hz, 1H), 8.04 (d, J = 3.3 Hz, 1H), 8.80 (s, 1H 1H NMR (DMSO-d6): d 1.56-1.68 (m, TH), 2.10-2.26 N4-Cyclobutyl-5- ( m, 4H), 2.21 (s, 3H), 2.44 (t, fluoro-N4-methyl-N2- 4H), 3.02 (t, J = 4.8 Hz, 4H), 1147 [4- (4- 3.05 (d, J = 2.7 Hz, 3H), 4.74 + methylpiperazine) phenyl] - (m, J = 7.8 Hz, 1H), 6.82 (d, 2,4-? Irimidindiamine J = 9.0 Hz, TH), 7.49 (d, J = 8.7 Hz, 2H), 7.88 (d, J = 6.6 Hz, 1H), 8.79 (br, 1H), 19F 1H NMR (DMSO-d6): d 1.19 (t, J = 7.2 Hz, 3H), 1.56- 1.69 (m, TH), T.01-T.T1 (m, N4-Cyclobutyl-N2- [4-4H), 3.06 (t, J = 4.8 Hz, 4H), (4-ethoxycarbonii-3.11 (d, J = 3.0 Hz, 3H), 3.50 1148 piperazin) phenyl] -5- + (t, 4H), 4.05 (q, J = 7.2 Hz, fluoro-N4-methyl-2, 4- 2H), 4.76 (m, J = 8.4 Hz, pyripidiamine 1H), 6.93 (d, J = 9.0 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H), 7.97 (d, No. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.57-1.70 (m, 2H) , 2.13-2.24 (m, 4H), 3.07 (t, J = 4.8 Hz, N4-Cyclobutyl-5-4H), 3.11 (d, J = 3.3 Hz, 3H), fluoro-N4-methyl-N2- 3.73 ( t, J = 4.5 Hz, 4H), 4.78 1149 (3-morpholinophenyl) -2,4- (m, J = 8.7 Hz, 1H), 6.57 (, pyrimidinediamine 1H), 7.08 (m, 2H), 7.24 (m , 1H), 7.98 (d, J = 6.9 Hz, 1H), 9.19 (br, 1H); CLEM: time ret. 1 H NMR (CDCB): d 1.66-1.78 (m, 2H), 2.15 (s, 3H), N2- [3- (4- 2.22 (m, 4H), 3.17 (d, J = 2.7 Acetylpiperazine) phenyl] - Hz, 3H), 3.22 (m, 4H), 3.62 1150 N4-cyclobutyl-5-fluoro- (t, J = 4.8 Hz, 2H), 3.77 (t, J = + N4-methyl-2.4- 5.1 Hz , 2H), 4.85 (m, J = 8.4 piripndmdiamine Hz, 1H), 6.58 (dd, J = 2.4, 8.1 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 8.1 Hz, 1H NMR (CDCB): d 1.63- 1.77 (m, 2H), 2.21 (, 4H), N4-Cyclobutyl-5- 2.45 (s, 3H), 2.72 (t, J = 4.8 fluoro-N4-methyl- N2- Hz, 4H), 3.13 (d, J = 3.9 Hz, 1151 [3- (4-3H), 3.32 (t, J = 4.8 Hz, 4H), + + methylpiperazine) phenyl] - 4.84 (m, J = 8.7 Hz, 1H), 6.56 2,4-pyrimidinediamine (dd, J = 2.4, 8.1 Hz, 1H), 6.82 (br, 1H), 7.00 (d, J = 8.1 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H NMR (DMSO-d6): d 1.19 (t, J = 7.2 Hz, 3H), 1.60-1.70 (m, 2H), 2.13-2.28 (m, N4-Cyclobutyl-N2- [3-4H ), 3.08 (t, J = 5.1 Hz, 4H), (4-ethoxycarbonyl-3.12 (d, J = 3.3 Hz, 3H), 3.50 1152 piperazine) phenyl] -5- + (t, 4H), 4.05 (q , J = 7.2 Hz, fluoro-N4-methyl-2,4-2H), 4.79 (, J = 9.0 Hz, pyrimidimethamine 1H), 6.59 (d, J = 6.9 Hz, 1H), 7.09 (m, 2H), 7.27 (s, 1H), 7.99 1H NMR (DMSO-d6): d 1.69-1.78 (m, 2H) , 2.28 (m, N2- (2-An? Inocarborul- 4H), 3.36 (d, J = 3.3 Hz, 3H), 5-benzoxy-4- 3.90 (s, 3H), 4.94 (, 1H), methoxyphenyl) -N4- 5.30 (s, 2H), 7.12 (s, 1H), 1153 cyclobutyl-5-fluoro-N4- 7.35-7.48 (m, 6H), 9.04 (d, methyl-2,4- J = 9.0 Hz, 1 HOUR); LCMS: pyrimidimethamine time ret: 11.25 min; purity: 98.01%; MS (m / e): 435.22 (M-16).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.62-1.74 (m, 2H), 2.02-2.15 (m, 2H), 2.23-2.31 (m, 2H), N2- (4-4.50 (, J = 8.1 Hz, 1H), Benzamidophenyl) -N4- 7.46-7.68 (m, 8H) , 7.84 (d, 1154 cyclobutyl-5-fluoro-2,4- J = 3.6 Hz, 1H), 7.92 (td, J = pyrimid diamine 1.2, 6.6 Hz, 2H), 8.99 (s, 1H), 10.07 (s) , 1 HOUR); 19 F NMR (282 MHz, DMSO-d6): d-167.01; LCMS: ret 1 H NMR (DMSO-d 6): d 1.54 (m, 4 H), 1.70 (m, 2 H), 1.94 (m, 2 H), 2.98 (t, J = 4.8 N 4 -cyclopentyl-5 Hz, 4 H) , 3.70 (t, J = 4.8 Hz, fluoro-N2- (4-4H), 4.30 (q, J = 6.9 Hz, 1H), 1155 + morpholinophenyl) -2.4-6.80 (d, J = 9.0 Hz, 2H), 7.22 pyrimidinediamine (d, J = 6.9 Hz, 1H), 7.55 (d, J = 9.3 Hz, 2H), 7.76 (d, J = 3.6 Hz, 1H), 8.74 (br, 1H); 19F 1 H NMR (DMSO-d 6): d 1.54 (m, 4H), 1.70 (, 2H), 1.93 (m, 2H), 2.02 (s, 3H), N2- [4- (4- 2.94 (t, J = 4.8 Hz, 2H), 3.01 Acetylpiperazine) phenyl] - (t, J = 5.1 Hz, 2H), 3.54 (t, 1156 N4-cyclopentyl-5H), 4.30 (q, J = 6.9 Hz, 1H), fluoro-2,4-6.83 (d, J = 8.7 Hz, 2H), 7.24 pyrimidinediamine (d, J = 7.2 Hz, 1H), 7.56 (d, J = 9.0 Hz, 2H), 7.76 (d, J = 3.9 1 H NMR (DMSO-d 6): d 1.54 (m, 4H), 1.70 (m, 2H), 1.93 (m, 2H), 2.21 (s, 3H), N4-Cyclopentyl-5- 2.44 (t, 4H), 3.01 (t, 4H), fluoro-N2- [4- (4- 4.30 (q, J = 6.3 Hz, 1H), 6.79 1157 + methylpiperazine) phenyl] - (d, J = 8.7 Hz, TH), l. TT (d, 2,4-? Ijrimidindiamine J = 6.3 Hz, 1H), 7.53 (d, J = 9.0 Hz, 2H), 7.76 (d, J = 3.0 Hz, 1H), 8.72 (br, 1H); NMR (28 1 H NMR (DMSO-d 6): d 1.52 (m, 4 H), 1.71 (m, 2 H), 1.93 (m, 2 H), 3.03 (t, J = 4.8 N 4 -cyclopentyl-5 Hz, 4 H) , 3.72 (t, J = 4.8 Hz, fluoro-N2- (3-4H), 4.36 (m, 1H), 6.45 (d, 1158 + morpholinophenyl) -2.4- J = 9.6 Hz, 1H), 7.02 ( t, J = pñ ± m ^ mdiamine 7.8 Hz, 1H), 7.13 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 7.2 Hz, 1H), 7.42 (s, 1H), 7.80 (d, J = 3.6 No. Compound Name Physical Data Triptase Triptase Triptase f_sik Com ID, LD, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.53 (m, 4H), 1.71 (m, 2H), 1.94 (m, 2H), 2.03 (s, 3H), N2- [3 - (4- 3.02 (t, J = 5.1 Hz, 2H), 3.08 Acetylpiperazine) phenyl] - (t, J = 4.8 Hz, 2H), 3.55 (t, 1159 N4-cyclopentyl-5H), 4.36 (q , J = 6.6 Hz, 1H), fluoro-2,4-6.47 (d, J = 7.8 Hz, 1H), 7.03 pirin? Dmdiamine (t, J = 8.1 Hz, 1H), 7.14 (d, J = 7.8 Hz , 1H), 7.30 (d, J = 7.2 N4-Cyclopentyl-5- CLEM: time ret .: 6.49 fluoro-N2- [3- (4-1160 min; purity: 79.17%; MS + methylpiperazine) phenyl] ~ (m / e): 371.23 (MH +). 2,4-pyrimidiamine N4-Cyclopentyl-N2- [3- (4-ethoxycarbonyl-LCMS: time ret: 10.76 1161 piperazin) phenyl] -5- min; purity: 77.07%; MS + fluoro-2,4- (m / e): 429.50 (MH +). pyrididinediamine 1H NMR (DMSO-d6): d 1.14 (m, 1H), 1.31 (m, 4H), 1.64 (d, 1H), 1.75 (m, 2H), N4-Cyclohexyl-5- 1.90 (, 2H), 2.98 (t, J = 4.8 fluoro-N2- (4 Hz, 4H), 3.71 (t, J = 4.8 Hz, 1162 morpholinophenyl) -2.4- 4H), 3.86 (m, 1H), 6.80 (d, piripudindiamine J = 9.3 Hz, 2H), 7.14 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 9.0 Hz, TH), 7.76 (d, J = 3.9 Hz, 1H), 8 1H NMR (DMSO -d6): d 1.31 (, 5H), 1.64 (d, 1H), 1.75 (, 2H), 1.90 (, 2H), N2- [4- (4- 2.02 (s, 3H), 2.94 (t, J = 4.8 Acetylpiperazine) phenyl] - Hz, 2H), 3.01 (t, J = 5.1 Hz, 1163 N4-cyclohexyl-5- 2H), 3.55 (m, 4H), 3.86 (m, + fluoro-2,4- 1H ), 6.82 (d, J = 9.0 Hz, 2H), pyrimidinediamine 7.12 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 1H NMR (DMSO- d6): d 1.31 (m, 5H), 1.64 (d, 1H), 1.75 (m, 2H), 1.90 (m, TH), N4-Cyclohexyl-5- 2.21 (s, 3H), 2.46 (t, J = 4.8 fluoro-N2- [4- (4- Hz, 4H), 3.01 (t, J = 4.8 Hz, 1164 methylpiperazin) phenyl] -4H), 3.85 (m, 1H), 6.79 (d, + + 2, 4-? Irinridmdiamine J = 9.0 Hz, TH), 7.12 (d, J = 8.4 H z, 1H), 7.52 (d, J = 9.0 Hz, TH), 7.76 (d, J = 3.9 Hz, 1H), 8 No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 1.19 (t, J = 7.2 Hz, 3H), 1.31 (m, 5H), 1.64 (d, 1H ), 1.76 N4-Cyclohexyl-N2- [4- (m, 2H), 1.90 (m, 2H), 2.97 (4-ethoxycarbonyl- (t, J = 4.8 Hz, 4H), 3.48 (t, 1165 piperazin) phenyl] -5- + + 4H), 3.86 (m, 1H), 4.04 (q, fluoro-2,4- J = 7.2 Hz, 2H) , 6.82 (d, J = pyridinediamine 9.0 Hz, 2H), 7.12 (d, J = 6.9 Hz, 1H), 7.55 (d, J = 9.3 Hz, 2H), 7 1 H NMR (DMSO-d6): d 1.27 ( m, 5H), 1.63 (d, 1H), 1.76 (m, 2H), 1.87 (m, 2H), N4-Cyclohexyl-5- 3.04 (t, J = 4.8 Hz, 4H), 3.72 fluoro-N2- ( 3-1166 (t, J = 4.8 Hz, 4H), 3.90 (m, + morpholinophenyl) -2.4- 1H), 6.46 (dd, J = 2.1, 7.8 Hz, pyru? Dmdiamine 1H), 7.03 (t, J = 8.4 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.24 (m, 2H), 7.80 (d, J = 3.9 Hz, 1H NMR (DMSO-d6): d 1.31 (, 5H) , 1.61 (m, 1H), 1.76 (m, 2H), 1.87 (m, 2H), N2- [3- (4- 2.03 (s, 3H), 3.04 (t, 2H), Acetylpiperazine) phenyl] - 3.09 (t, 2H), 3.56 (t, 4H), 1167 N4-cyclohexyl-5- + 3.90 (m, 1H), 6.48 (d, J = 9.0 fluoro-2.4-Hz, 1H), 7.04 (t, J = 8.4 Hz, pyrimid diamine 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.25 (m, TH), 7.80 (d, J = 3.6 Hz, 1H NMR (DMSO-d6): d 1.14 (m , 1H), 1.31 (m, 4H), 1.63 (d, 1H), 1.76 (m, 2H), N4-Cyclohexyl- 5- 1.86 (m, 2H), 2.26 (s, 3H), fluoro-N2- [3- (4- 3.09 (t, 4H), 3.32 (t, 4H), 1168 methylpiperazine) feml] - 3.88 (m, 1H), 6.45 (d, J = 6.9 2,4-pyriridinediamine Hz, 1H), 7.01 (t, J = 8.1 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 7.24 (m, 2H) , 7.80 (d, J = 3.9 Hz, 1H NMR (DMSO-d6): d 1.19 (t, J = 6.9 Hz, 3H), 1.31 (m, 5H), 1.62 (d, 1H), 1.76 N4-Cyclohexyl- N2- [3- (m, 2H), 1.87 (m, 2H), 3.05 (4-ethoxycarbonyl- (t, J = 4.8 Hz, 4H), 3.49 (t, 1169 piperazin) phenyl] -5- + 4H) , 3.90 (m, 1H), 4.05 (q, fluoro-2,4- J = 7.2 Hz, 2H), 6.48 (d, J = pyrinidinediamine 4.5 Hz, 1H), 7.03 (t, J = 8.1 Hz, 1H) , 7.16 (d, J = 6.6 Hz, 1H), 7 No. Compound Name Physical Data Triptase Triptase Tftasa f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.57 (m, 4H), 1.72 (m, 2H), 1.96 (m, 2H), 4.32 (q, J = 7.5 N2- (4 Hz, 1H), 7.29 (d, J = 6.3 Hz, Benzamidophenyl) -N4- 1H), 7.46-7.69 (m, 7H), 7.81 1170 cyclopentyl-5-fluoro- (d, J = 3.9 Hz, 1H), 7.92 (d, 2,4-pyrimid-diamine) J = 9.6 Hz, 2H), 8.97 (s, 1H), 10.05 (s, 1H); 19 F NMR (282 MHz, DMSO-d 6): d-166.85; LCMS: 1 H NMR (DMSO-d 6): d 1.60 (m, 4 H), 1.74 (m, 2 H), 1.96 (, 2 H), 3.85 (s, 3 H), N 2 - (2-Aminocarbonyl- 4.43 (q, J = 6.9 Hz, 1H), 5.24 5-benzoxy-4- (s, 2H), 7.06 (s, 1H), 7.31-1171 methoxyphenyl) -N4- + 7.50 (, 6H), 8.53 (d, J = 7.2 cycle ? entyl-5-fluoro-Hz, 1H), 8.70 (d, J = 6.9 Hz, 2,4-pyrimidinediamine 1H); 19 F NMR (282 MHz, DMSO-d 6): d-155.92; LCMS: ret time: 1H NMR (DMSO-d6): d 1.55 (m, 4H), 1.71 (m, 2H), 1.94 (m, 2H), 3.09 (s, 3H), N2- [4- (N- Acetyl-N- 3.31 (s, 3H), 4.32 (q, J = 7.2 methyamin) phenyl] -N4-Hz, 1H), 7.13 (d, J = 9.0 Hz, 1172 cyclopentyl-5-fluoro-2H), 7.34 (d, J = 7.2 Hz, 1H), 2,4-pyrimidinediamine 7.77 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 3.9 Hz, 1H), 9.14 (s, 1H); 19 F NMR (282 MHz, DMSO-d 6) 1 H NMR (DMSO-d 6): d 1.55 (m, 4 H), 1.71 (m, 2 H), 1.93 (m, 2 H), 3.62 (s, 4 H), N 4-Cyclopentyl -5- 4.31 (q, J = 6.6 Hz, 1H), 6.71 fluoro-N2- [3- (N-2- (d, J = 7.8 Hz, 1H), 7.25 (t, 1173 imidazolin-2- J = 7.8 Hz, 1H), 7.40 (d, J = il) aminophenyl] -2.4- 7.2 Hz, 1H), 7.53 (d, J = 7.5 pi? Nidindiamine Hz, 1H), 7.84 (s, TH), 8.22 (s, 1H), 9.23 (s, 1H), 10.54 (br, l 1H NMR (DMSO-d6): d 1.33 (m, 5H), 1.65 (d, 1H), 1.78 (m, 2H), 1.92 ( m, TH), 3.88 (m, N2- (4-1H), 7.22 (d, J = 8.1 Hz, 1H), Benzamidophenyl) -N4- 1174 7.46-7.69 (m, 1H), 7.81 (d, J = + + cyclohexyl-5-fluoro- 3.9 Hz, 1H), 7.92 (d, J = 6.6 Hz, 2,4-p-methylindyamine TH), 8.99 (s, 1H), 10.05 (s, 1H); 19F NMR (282 MHz , DMSO-d6): d- 166.98; CL No. Compound Name Physical Data Triptase Triptase Tftasa f sik Com ID, ID, ID, CMC Lpt, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T 1H NMR (DMSO-d6): d 1.36 (m, 5H), 1.65 (d, 1H), 1.79 (m, 2H), 1.88 (m, 2H), N2- (2-Aminocarbonyl-3.85 (s, 3H), 4.05 (m, 1H), 5-benz oxy-4- 5.24 (s, 2H), 7.06 (s, 1H), 1175 methoxyphenyl) -N4- 7.31-7.50 (m, 6H), 8.44 (d, cyclohexyl-5-fluoro- J = 7.5 Hz, 1H) , 8.70 (d, J = 2,4-pirm? Idindiamine 6.9 Hz, 1H); 19 F NMR (282 MHz, DMSO-d 6): d-156.00; CLEM: time ret. 1 H NMR (DMSO-d 6): d 1.32 (m, 5 H), 1.64 (d, 1 H), 1.74 (, 2 H), 1.90 (m, TH), N 2 - [4- (N-Acetyl-N-3.09 ( s, 3H), 3.32 (s, 3H), methylamino) phenyl] -N4- 3.88 (m, 1H), 7.13 (d, J = 8.4 1176 cyclohexyl-5-fluoro-Hz, 2H), 7.26 (d, J = 7.5 Hz, 2,4-pyriridiamine 1H), 7.75 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 3.9 Hz, 1H), 9.15 (s, 1H); 19 F NMR (282 MHz, DMSO- N 4 -Cyclohexyl-5-fluoro-N 2 - [3- (N-2-LCMS: ret time: 6.42 1177 imidazoline-2 min, purity: 86.49%, IM il) aminophenyl] -2.4- (m / e): 370.47 (MH +). Pyrimidinediamine 1H NMR (DMSO-d6): d 7.22 (t, J = 7.8 Hz, 1H), 7.31 (d, J = 9.3 Hz, 2H), 7.40 (t, N2, N4-Bis [3- (oxazole-J = 8.1 Hz, 1H), 7.46 (d, J = 1178 2-ü) phenyl] -5-fluoro-2.4-7.5 Hz, 1H) , 7.64 (d, J = 7.5 pijrimidindiamine Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 8.08 (d, J = 7.5 Hz, 1H), 8.11 (d, 2H), 8.18 (d, J = 3.6 Hz, 1H), 8.24 (t, J = 1.8 Hz, 1 1 H NMR (DMSO-d6): d 1.53-1.71 (, 2H), 2.11-2.32 (m, 4H), 3.16 (d, J = 3.6 Hz, N4-Cyclobutyl-5- 3H), 4.89 (m, J = 8.4 Hz, fluoro-N4-methyl-N2- 1H), 7.36 (d, J = 0.9 Hz, 1H), 1179 [3- (oxazole- 2-yl) phenyl] - 7.40 (t, J = 7.8 Hz, 1H), 7.57 2,4-pyrimidinediamine (m, 2H), 8.06 (d, J = 7.2 Hz, 1H), 8.20 (d, J = 0.9 Hz, 1H), 8.57 (t, J = 1.8 Hz, 1H), 9.68 (s, No. Name of Compound Physical Data Triptase Triptase Triptase f_sik Com ID, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE , 8pt Ion, 3pt 1 H NMR (DMSO-d 6): d 1.83 (m, 1H), 2.16 (m, 1H), 2.40 (dd, J = 5.1, 9.3 Hz, 1H), (S) -N4- (l - 2.58 (m, TH), 2.89 (dd, J = Benzylpyrrolidin-3-yl) - 7.2, 9.3 Hz, 1H), 2.99 (t, J = 1180 5-fluoro-N2- (4- + 4.8 Hz, 4H ), 3.58 (d, J = 1.8 morpholinophenyl) -2.4-Hz, 2H), 3.72 (t, J = 4.8 Hz, pyrimidinediamine 4H), 4.41 (m, 1H), 6.78 (d, J = 9.0 Hz, TH), l.TT (m, 1H), 7.2 1 H NMR (DMSO-d6): d 1.81-1.87 (m, 1H), 2.03 (s, (S) -N2- [4- (4-3H), 2.14-2.23 (m, 1H), 2.40 Acetylpiperazin) phenyl] - (dd, J = 5.7, 9.6 Hz, 1H), 2.56 1181 N4- (l-benzylpyrrolidin- (m, 2H), 2.89 (dd, J = 7.2, 9.3 + 3-yl) -5-fluoro-2,4-Hz, 1H), 2.95 (t, J = 5.1 Hz, pyrimidinediamine 2H), 3.02 (t, J = 5.1 Hz, 2H), 3.55 ( m, 4H), 3.58 (s, 2H), 4.41 (m, 1H), 6.81 (d, J = 9.0 (S) -N4- (l- B encylpyrrolidin-3-yl) -MSC: time ret: 1.17 1182 5-fluoro-N2- [4- (4- min.; purity: 95.41%; EM methylpiperazine) fenne] - (m / e): 462.15 (MH +). 2,4-pyrinidinediamine 1H NMR (DMSO-d6): d 1.19 (t, J = 7.2 Hz, 3H), 1.83 (S) -N4- (l- (m, 1H), 2.17 (m, 1H), 2.40 Benzylpyrrolidin-3-yl) - (dd, J = 5.1, 9.0 Hz, 1H), 2.56 TST2- [4- (4-1183 ethoxycarbonylpiperazine) (m, 2H), 2.89 (dd, J = 7.2, 9.0 + Hz, 1H), 2.98 (t, J = 5.1 Hz, fenne] -5-fluoro-2,4- 4H), 3.49 (t, J = 5.1 Hz, 4H), pyrimidinediainine 3.58 (d, J = 1.8 Hz, TH) , 4.05 (q, J = 7.2 Hz, 2H), 4.44 ((S) -N4- (1-Benzylpyrrolidin-3-yl) -MSCM: time ret: 6.81 1184 5-fluoro-N2- (3 min; purity: 100%; MS morpholinfe? il) -2.4- (me): 449 (MH +). pyrimidinediamine 1H NMR (DMSO-d6): d 1.82-1.88 (m, 1H), 2.02 (s, (S ) -N2- [3- (4-3H), 2.16-2.26 (m, 1H), 2.37 Acetylpiperazine) phenyl] - (dd, J = 5.7, 9.0 Hz, 1H), 2.56 1185 N4- (benzylpyrrolidin-3) (m, 2H), 2.92 (dd, J = 6.9, 9.0 + il) -5-fluoro-2,4-Hz, 1H), 3.03 (t, J = 5.1 Hz, pyrimidinediamine 2H), 3.10 (t, J) = 5.1 Hz, 2H), 3.56 (m, 4H), 3.58 (s, TH), 4.53 (m, 1H), 6.47 (d, J = 8.4 No. Compound Name Physical Data Triptase Triptase Tript asa f_sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt (S) -N4- (l- Bencilpirrohdin-3-il) - CLEM: Ret. time: 2.79 1186 5 -fluoro-N2- [3- (4- min; purity: 97.87%; MS + methylpiperazine) phenyl] - (m / e): 462 (MH +). 2,4-pyrimidindiamine 1H NMR (DMSO-d6): d 1.18 (t, J = 7.2 Hz, 3H), 1.82 (S) -N4- (l- (, J = 6.5 Hz, 1H), 2.19 (m, Benzylpyrrolidin-3-yl) - 1H), 2.37 (dd, J = 5.7, 9.0 Hz, N2- [3- (4-1H), 2.56 (m, 2H), 2.91 (dd, 1187 ethoxycarbonylpiperazine) J = 7.2, 9.0 Hz, 1H), 3.06 (t, phenyl] -5-fluoro-2,4- J = 5.1 Hz, 4H), 3.51 (t, J = pyrimidinediamine 5.1 Hz, 4H), 3.58 (s, 2H), 4.04 (q, J = 7.2 Hz, 2H), 4.55 (1H NMR (DMSO-d6): d 1.61-1.73 (m, 2H), 2.01-2.14 N4-Cyclobutyl-5- (m, 2H), 2.25-2.33 ( m, 2H), fluoro-N2- [3-chloro-4- 2.29 (s, 3H), 2.55 (m, 4H), 1188 (4-methylpiperazin) -2.91 (t, 4H), 4.47 (m, J = 8.1 phenyl] -2.4-Hz, 1H), 7.03 (d, J = 8.7 Hz, pyrimidinediamine 1H), 7.43 (dd, J = 2.7, 9.0 Hz, 1H), 7.69 (d, J = 7.2 Hz, 1H ), 7.84 (d, J = 3.6 Hz, 1H), 8.07 1 H NMR (DMSO-d6): d P-acid salt 2.28 (s, 6H), 2.86 (d, J = 4.8 toluenesulfonic Bis of Hz, 3H) , 2.92 (m, 2H), 3.13 N4- (3,4-Dihydro- (q, J = 10.8 Hz, 2H), 3.49 (m, 2H, 4H-5-4H), 3.74 (d, J = 13.2 Hz , 1189 pyrid [1,4] oxazin-6-yl) -2H) , 4.15 (t, J = 4.2 Hz, 2H), + 5-fluoro-N2- [3- (4-6.66 (d, J = 7.8 Hz, 1H), 6.96 methylpiperazin) phenyl] - (d, J = 8.7 Hz, 1H), 7.08 (d, 2,4-pyrimidiamine J = 8.4 Hz, 4H), 7.17 (m, 4H), 7. 1 H NMR (DMSO-d6): d 2.81 chloride salt (d, J = 4.5 Hz, 3H), 3.08 Bis hydrogen of N4- (m, 4H), 3.48 (d, J = 11.7 Hz, (3,4-Dihydro-2H, 4H-5- 2H), 3.55 (t, 2H) , 3.72 (d, J = 1190 pyrid [1,4] oxazin-6-yl) - 11.7 Hz, 2H), 4.18 (t, J = 4.2 + + 5-fluoro-N2- [3- (4- Hz, 2H), 6.65 (d, J = 9.0 Hz, methylpiperazin) phenyl] - 1H), 6.74 (d, J = 8.1 Hz, 1H), 2,4-pyrimidiamine 7.15 (t, J = 8.1 Hz, 1H) , 7.36 (d, J = 8.1 Hz, 1H), 7.41 No. Compound Name Physical Data Triptase Tftase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 1.14 (m, 1H), 1.33 (m, 4H), 1.63 (d, 1H), 1.74 (m, 2H), N2- [3-Chloro-4- (4-1.90 ( m, TH), 2.21 (s, 3H), methylpiperazine) phenyl] -2.45 (m, 4H), 2.88 (t, 4H), 1191 N4-cyclohexyl-5- + 3.89 (m, 1H), 7.01 (d, J = 8.7 + fluoro-2,4-Hz, 1H), 7.2 4 (d, J = 7.8 Hz, 1H), 7.39 (dd, J = 2.4, 8.4 Hz, 1H), 7.81 (d, J = 3.9 Hz, 1H), 8.0 1H NMR (DMSO-d6): d 1.65- 1.76 (m, 2H), 2.04 (s, 3H chloride salt), 2.08-2.26 (m, 4H), 3.10 hydrogen Bis of N2- (t, 2H), 3.17 (t, 2H), 3.58 (t, [4- (4-4H), 4.43 (m, J = 7.8 Hz, 1192 + Acetylpiperazine) phenyl] -1H), 7.02 (d, J = 8.1 Hz, TH), N 4 -cyclobutyl-5-fluoro-7.37 ( d, J = 8.4 Hz, 2H), 8.00 2,4-pyrimidinediamine (d, J = 5.1 Hz, 1H), 9.10 (br, 1H), 10.02 (br, 1H); 19 F NMR (2 1 H NMR (DMSO-d 6): d 1.24 (m, 4 H), 1.37 (q, 1 H), p-1.62 (d, 1 H), 1.76 (d, 2 H), toluenesulfonic acid salt of Bis of 1.85 (d, 2H), 2.28 (s, 6H), N4-Cyclohexyl-5- 2.86 (d, J = 3.9 Hz, 3H), 2.92 1193 fluoro-N2- [4- (4- (d, 2H), 3.15 (m, 2H), 3.52 methylpiperazine) phenyl] - (d, 2H), 3.80 (d, 3H), 7.00 2,4-pyrimidiamine (d, J = 9.3 Hz, 2H), 7.09 (d, J = 7.8 Hz, 4H), 7.36 (d, J = 9.3 Hz, 1 H NMR (DMSO-d 6): d 1.33 (m, 5H), 1.61 (d, 1H), chloride salt of 1.77 (d, 2H), 1.87 (d, 2H), hydrogen Bis of N4- 2.79 (d, J = 4.8 Hz, 3H), 3.09 Cyclohexyl-5-fluoro- (m, 4H), 3.47 (d, 2H), 3.78 1194 + N2- [4- (4- (d, 2H ), 3.83 (m, 1H), 7.01 methylpiperazine) phenyl] - (d, J = 9.0 Hz, 2H), 7.39 (d, 2,4-pyrimidinediamine J = 9.0 Hz, 2H), 8.10 (d, J = 5.4 Hz, 1H), 9.08 (d, J = 8.1 Hz, 1H) lH NMR (DMSO-d6): d 1.55 (m, 4H), 1.71 (m, 2H), N2- [3-Chloro-4- (4 - 1.98 (m, 2H), 2.31 (s, 3H), methylpiperazine) phenyl] - 2.57 (m, 4H), 2.91 (t, 4H), 1195 N4-cyclopentyl-5- 4.30 (q, J = 6.9 Hz, 1H), 7.03 + fluoro-2,4- (d, J = 8.7 Hz, lH), 7.36 (d, J = pyrimid diamine 6.9 Hz, lH), 7.43 (dd, J = 2.7, 9.0 Hz, 1H), 7.82 (d, J = 3.9 Hz, 1H), 8.07 (d, J = 2.4 Hz, No. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d 0.69 (m, 2H), 0.91 (m, 2H), 1.87 (m, 1H), 2.22 (s, 3H), N2- [3 -Cloro-4- (4- 2.46 (m, 4H), 2.90 (t, 4H), methylpiperazin) phenyl] - 6.31 (br, 1H), 7.04 (d, J = 9.0 1196 N4- (3-cyclopropyl-1H - Hz, 1H), 7.51 (br, 1H), 7.79? Irazol-5-il) -5-fluoro- (s, 1H), 8.02 (s, 1H), 9.14 (br, 1H), 9.52 (br, 1H), 12.07 (br, 1H); 19 F NMR (282 MHz, DMSO 1 H NMR (DMSO-d 6): d N 2 - [3-Chloro-4- (4- 2.21 (s, 3 H), 2.45 (t, 4 H), methylpiperazine) phenyl] - 2.88 (t , 4H), 3.39 (m, 2H), N4- (3,4-dihydro-4.09 (t, J = 4.2 Hz, 2H), 6.53 1197 2H, 4H-5- (s, 1H), 6.94 (d, J = 8.7 Hz, + pyrid [1,4] oxazin-6-yl) -1H), 7.01 (d, J = 8.7 Hz, 1H), 5-fluoro-2,4-7.12 (d, J = 8.4 Hz , 1H), 7.46 pyrimidiamine (dd, J = 2.7, 8.7 Hz, 1H), 7.84 (d, J = 2.7 Hz, 1H), 8.04 (d, 1H NMR (DMSO-d6): d 1.67-1.76 (m, 2H), 2.11-2.18 Chloride salt of (m, 2H), 2.25-2.31 (, 2H), hydrogen Bis of N2- 2.82 (d, J = 4.5 Hz, 3H), [3-Chloro-4- (4 - 3.02-3.20 (m, 4H), 3.35 (m, 1198 + methylpiperazine) phenyl] -2H), 3.48 (m, TH), 4.44 (m, N4-cyclobutyl-5-fluoro-J = 7.5 Hz, 1H) , 7.18 (d, J = 2,4-? Mmidindiamine 8.7 Hz, 1H), 7.40 (dd, J = 2.4, 8.7 Hz, 1H), 7.97 (d, J = 2.1 Hz, 1H), 1H NMR (DMSO- d6): d 1.17 (m, 1H), 1.36 (m, 4H), chloride salt of 1.63 (d, 1H), 1.78 (m, 2H), hydrogen Bis of N2- 1.86 (m, 2H), 2.83 ( d, J = 4.8 [3-Chloro-4- (4 Hz, 3 H), 3.00-3.20 (m, 4H), 1199 methylpiperazine) phenyl] - + 3.34 (m, 2H), 3.48 (, 2H), N4-cyclohexyl-5-3.87 (m, 1H), 7.16 (d, J = 8.7 fluoro-2.4-Hz , 1H), 7.36 (dd, J = 2.4, 9.0 pyrimid diamine Hz, 1H), 7.96 (d, J = 2.4 Hz, 1H) N4-Cyclopentyl-5-fluoro-N2- [3-methyl-4-CLEM: Ret. time: 9.70 1200 (4- min .; purity: 89.34%; MS + methylpiperazine) phenyl] - (m / e): 385 (MH +). 2,4-pi? Nid diamine N4-Cyclohexyl-5-fluoro-N2- [3-methyl-4- CLEM: ret time: 11.34 1201 (4 min, purity: 94.34%, EM + methylpiperazine) phenyl] - (m / e): 399.24 (MH +). 2,4-pM idindiamine No. Compound Name Physical Data Triptase Tftase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (3-Cyclopropyl-1H- pyrazol-5-yl) -5-fluoro-CLEM: retentate time: 10.35 1202 N2- [3-methyl-4- (4- ruin, purity: 96.72%, EM + + methylpiperazin) phenyl] - ( m / e): 423 (MH +). 2,4-pyrimidimediamine N4- (3,4-Dihydro-2H, 4H-5-pyrid [1,4] oxazin-6-yl) - CLEM: time ret: 10.77 1203 5-fluoro-N2- [3-methyl] - min .; purity: 93.79%; MS + + 4- (4- (m / e): 451 (MH +). Methylpyridin) femyl] -2,4-pyrirm'dmdiamine N 4 - (3-Cyclopropyl-1H-pyrazol-5-yl) -5 -fluoro-CLEM: time ret: 10.35 1202 N2- [3-methyl-4- (4- min, purity: 96.72%, MS + methylpiperazine) phenyl] - (m / e): 423 (MH +). 2,4-pyrimidiamine N4- (3,4-Dihydro-2H, 4H-5-pyrid [1,4] oxazin-6-yl) -MSCM: time ret .: 10.77 1203 5-fluoro-N2- [3- methylmin; purity: 93.79%; MS + 4- (4- (m / e): 451 (MH +) .methylpiperazine) phenyl] -2,4-pyrimidinediamine 5-Fluoro-N 4 -isopropyl-CLEM: ret. Time: 3.64 N 2 - [4- (4 - 1204 min, purity: 95.29%, EM + metü? Iperazin) phenyl] - (me): 345 (MH +). 2,4-? Irididiamine N2- [3-Chloro-4- (4- CLEM: time-off: 5.14 methylpiperazine) phenyl] -205 min; purity: 92.47%; 5-Fluoro-N 4 -isopropyl- (m / e): 379 (MH +). 2,4-p-tidindindiamine 5-Fluoro-N4-isopropyl-CLEM: time ret .: 1.99 N2- [3-methyl-4- (4-120 min, purity: 93.17%, EM methylpiperazine) phenyl] - (m / e): 359 (MH +). 2,4-pyrimidiamine N4-Cyclobutyl-5-fluoro-N2- [4- (4- CLEM: ret. Time: 15.09 1207 methylpiperazin) -3- min; purity: 94.19%; MS + trifluoromethylphenyl] - (m / e): 425 (MH +). 2,4-pyrimidiamine N4-Cyclopentyl-5-fluoro-N2- [4- (4-CLEM: ret time: 15.32-1208 methylpiperazin) -3- min; purity: 92.83%; Trifluoromethylphenyl EM - (m / e): 439.30 (MH +). 2,4-pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 5-Fluoro-N4-isopropyl- N2- [4- (4- CLEM: time ret .: 7.29 1210 methylpiperazin) -3- min; purity: 88.24%; EM trifluoromethylphenyl] - (m / e): 413.05 (MH +). 2,4-pyrimidine-idiamine N4- (3-Cyclopropyl-1H-pyrazol-5-yl) -5-fluoro-CLEM: time ret .: 8.27 N2 - [(4-1211 min, purity: 94.19%; + methylpiperazin) -3- (m / e): 477 (MH +). trifluoromethyphenyl] -2,4-pyrimidimediamine 2-chloro-5-fluoro-N4-CLEM: ret time: 9.57 (1.2.2.6.6-1212 min, purity: 90.78%; EM? enmethylpiperidin-4-) (m / e): 301.19 (MH +). ü) -4-pirintidmamin 2-chloro-N4- (l-CLEM: ret. time: 10.29 ethoxycarbomlpiperidin- 1213 min.; purity: 94%; MS 4-yl) -5-fluoro-4- (m / e): 303.04 (MH +). pyrmudmamine 5-Fluoro-N 4 -isopropyl-LCMS: time ret: 4.63 N2- [3- (4-1214 min, purity: 97.16%, methylpperazin EM) phenyl] - (m / e): 345.41 (MH +). 2,4-pirinn ^ diarnin 80 1215 EM N4-tert-Butyl-5-fluoro-CLEM: ret time: 7.81 N2- [3- (4-1216 min, purity: 94.56%, EM methylpiperazine) phenyl] - ( me): 359.23 (MH +). 2,4-pirintidmdiarnina N4-tert-Butü-N2- [3-chloro-4- (4- CLEM: ret. Time: 10.53 1217 methylpiperazin) phenyl] -min; purity: 93.25%; MS 5-fluoro-2,4- (m / e): 393 (MH +). pyrimidmdiamine N4-tert-Butyl-5-fluoro-CLEM: time ret .: 4.35 N2- [3-metü-4- (4-1218 min, purity: 87.23%, EM methylpiperazine) phenyl] - (m / e): 373.26 (MH +). 2,4-pyripididiamine 5-Fluoro-N2- [4- (4-methylpiperazin) phenyl] -MSCM: time ret .: 1.30 N4- (1, 2.2.6.6- 1219 min., Purity: 95.14%; EM pentamethylpiperidin-4- (m / e): 456.63 (MH +). Ü) -2,4-pyrimidine diamine No. Name of Compound Physical Data Tftase Tftase Tftasa f sik Com ID, ID, ID, llpt CMC, CMC, CMC , IgE, 3pt IgE, 8pt Ion, 3pt N4-Cyclobutyl-5-fluoro-N2- [3-methyl-4-CLEM: ret time: 9.16 1220 (4-methylpiperazin) -min; Purity: 93.00%; Phenyl MS] -2.4- (m / e): 371.26 (MH +). pyriniin? n-diamine methylpiperazin) phenyl] -MSCM: time ret .: 1.40, N4- (1, 2,2,6,6-1221 1.71 min., purity: 95%; EM pentamethylpiperidin-4- (m / e) : 456.30 (MH +). Ü) -2,4- piirimddmdiamine N2- [3-Chloro-4- (4-methylpiperazin) phenyl] -MSCM: time ret: 1.44, 5-fluoro-N4- (l, 2.2 6.6-1222 1.74 min, purity 97%, EM pentamethylpiperidin-4- (m / e): 490.11 (MH +). Il) -2,4-pyrylimidiamine 5-Fluoro-N2- [3-methyl- 4- (4-methylpiperazin) -MSC: time ret: 1.46, fenu] -N4- (1, 2.2.6.6-1223 2.03 min, purity: 100%, pentamethylpiperidin-4-EM (m / e): 470.29 (MH +). il) -2,4- pyrimidindiamine 5-Fluoro-N4- (1,2,2,6,6-pentamethylpiperidin-4-CMS: time ret .: 1.46, 1224 il) - N2- [3- 2.70 min; purity: 97%; EM trifluoromethyl-4- (4- (m / e): 524.23 (MH +) .methylpiperazin) fenu] -piperidin-4-yl) -5- CLEM: ret. Time: 6.13 1225 fluoro-N2- [4- (4 - mine, purity: 95.45%; EM + methylpi? erazin) feml] - (m / e): 458 (MH +). 2,4-pyrimidinediamine N 4 - (l-Ethoxycarbonyl-piperidin-4-yl) -5-LCMS: retentate time: 9.94 1226 fluoro-N 2 - [3- (4 min, purity: 97%; methylphenyl EM? erazin) phenyl] - (m / e): 458.27 (MH +). 2,4-? Irimidindiamine N2- [3-Chloro-4- (4-methy1perazine) feml] - N4- (l-ethoxycarbonyl-CLEM: ret time: 14.71 1227 min., Purity: 98.79%; ME + piperidin-4 -il) -5- (m / e): 492 (MH +). fluoro-2,4-pyrirm'dmdiamine No. Name of Compound Physical Data Tftase Tftase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (1-Ethoxycarbonylpiperidine) - LCMS: time ret .: 9.26 4-yl) -5-fluoro-N2- [3-1228 min; purity: 97.16%; MS + methyl-4- (4- (m / e): 472 (MH +), methylpiperazin) phenyl] -2,4-pyrimidinediamine N 4 - (1-Ethoxycarbonylpiperidine-CLEM: ret time: 15.48 4-yl) -5- fluoro-N2- [4-1229 min; purity: 97.96%; MS + (4-methylpiperazine) -3- (m / e): 526 (MH +). trifluoromethylphenyl] -2,4-p? imdindiamine N4-Cyclobutyl-N2- [2-CLEM: ret. time: 5.52 (4-ethylpiperazine)? irid- 1230 min; purity: 94.98%; MS + 5-yl] -5-fluoro-2,4- (m / e): 372 (MH +). pyrimidinediamine N4-Cyclopentyl-N2- [2-CLEM: ret time: 6.27 (4-ethylpiperazine)? irid-1231 min; purity: 90.61%; MS + 5-yl] -5-fluoro-2,4- (m / e): 386.36 (MH +). p? ii ^ mydiamine N4-Cyclohexyl-N2- [2-CLEM: ret. time: 6.83 (4-ethylpiperazin) pyrid-1232 min; purity: 97.62%; MS + 5-yl] -5-fluoro-2,4- (m / e): 400 (MH +). pyrimidmdiamine N4-tert-Butyl-5-fluoro-N2- [4- (4- CLEM: ret. time: 15.37 1233 methylpiperazin) -3- min; purity: 96.00%; MS + trifluoromethylphenyl] - (m / e): 427 (MH +). 2,4-pyrimidinediamine N2- [2- (4-ethylpiperazine) pyrid-5-CLEM: ret. Time: 1.44, 1234 il] -5-fluoro-N4- 1.80 ruin; purity: 96%; MS isoprop-2,4- (m / e): 360.28 (MH +). pyrimidine diamine N4-Cyclobutyl-5-fluoro-N2- [3-CLEM: retentate time: 1.82 1235 hydroxymethyl-4- (4 min, purity: 90%, ME metipiperazine) phenyl] - (m / e): 387.14 (MH +). 2,4-pijrirm'dindiamine N4-tert-Butyl-N2- [2-CLEM: ret time: 4.27 (4-ethylpiperazin) pyrid-1236 min.; purity: 100%; MS 5-ü] -5-fluoro-2,4- (m / e): 374.18 (MH +). pyrimidinediamine N2- [2- (4-ethylpiperazine) pyrid-5-CLEM: ret. time: 1.27 il] -5-fluoro-N4- 1237 min; purity: 99.58%; MS (1,2,2,6,6-pentamethyl- (m / e): 471.73 (MH +). Piperidin-4-yl) -2,4-pyrin? Lmdiamine No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (l- Etoxicarborulpiperidin- CLEM: ret time: 7.03 4-il) -N2- [2- (4- 1238 min., Purity: 94.74% »; ethylpiperazin EM) pyrid-5 (m / e): 473 (MH +). il] -5-fluoro-2,4-pnunidinediamine N4-Cyclobutyl-5-fluoro-N2- [2- (4- CLEM: ret time: 9.65 1239 methypiperazin) -3- min; purity: 97.08%; Methylpyrid-5-yl] -2.4- (m / e): 372.11 (MH +). pyrimidim diamine N4-Cyclopentyl-5-fluoro-N2- [2- (4-CLEM: retentate time: 10.50 1240 methylpiperazin) -3- min; purity: 91.36%; MS + methylpyrid-5-yl] -2.4- (m / e): 385.85 (MH +). puimid diarynin N4-Cyclohexyl-5-fluoro-N2- [2- (4- CLEM: time ret .: 9.22 1241 methylpiperazin) -3- min; purity: 93.96%; Methylpyrid-5-yl] -2.4- (m / e): 400.11 (MH +). pyrimid diamine 5-Fluoro-N 4 -isopropyl-N 2 - [2- (4-CLEM: retentate time: 4.21 1242 methylpiperazin) -3- min; purity: 91.67%; Methylpyrid-5-yl] -2,4- (m e): 360.15 (MH +). pyrimidinediamine Hydrogen chloride salt Bis of N4- Cyclobutyl-5-fluoro-CLEM: time ret: 1.43, 1243 N2- [3-hydroxymethyl-4- 1.85 min; purity: 94%; MS (4-methyl? Iperazin) - (m / e): 387.05 (MH +). phenyl] -2,4- pyrimidindiamine 5-Fluoro-N2- [2- (4-methylpiperazin) -3-methylpyrid-5-yl] -N4-CLEM: time ret .: 7.05 1244 (1,2,2,6 , 6- min., Purity: 95.56%; EM pentamethylpiperidin-4- (m / e): 471.26 (MH +). Il) -2,4- pyrimidindiamine N 4 -cyclobutyl-5-fluoro-N 2 - [2- (4 LCMS: time ret: 9.37 1245 methylpiperazine) -4- min; purity: 92.45%; Methylpyrid-5-ñ] -2.4- (m / e): 371.99 (MH +). pyrazidinediamine N4-Cyclopentyl-5-fluoro-N2- [2- (4-CLEM: retentate time: 10.12 1246 methylpiperazin) -4- min; purity: 95.69%; EM methandid-5-yl] -2.4- (m / e): 386.09 (MH +). pyrimidindiamine No. Name of Compound Physical Data Tftase Tftase Triptase f sik Com ID, ID, ID, Cpt CMC, CMC, CMC, IE, 3pt IgE, 8pt Ion, 3pt N4-Cyclohexyl-5-fluoro-N2- [2- ( 4- LCMS: time ret .: 10.35 1247 methylpiperazin) -4- min .; purity: 92.30%; Methylpyrid-5-yl] -2,4- (m / e): 400.13 (MH +). pyrimidmdiamine 5-Fluoro-N4-isopropyl-N2- [2- (4- CLEM: ret time: 6.77 1248 methylpiperazin) -4- min; purity: 84.20%; Methylpyrid-5-yl] -2.4- (m / e): 359.97 (MH +). pirm dindiamine 5-Fluoro-N2- [2- (4-methylpiperazin) -4- methylpyrid-5-yl] -N4-CLEM: ret. time: 1.48, 1249 (1,2,2,6,6- 2.77 min., Purity: 98%> EM? Enmethyl? Iperidin-4- (m / e): 471.22 (MH +). Ü) -2,4- piri idindiamine 5-Fluoro-N4- (l-hydroxymethylcyclopentyl) LCMS: ret time: 11.16 1250 l-il) -N2- [3-methyl-4- (4- rain, purity: 99.47%, MS + metfiperazin) phenyl] - (m / e): 415.57 (MH +). 2,4-? Irirnidindiamine N4- (5-Amiuo-l, 2,4-triazol-3-yl) -5-fluoro-N2- [3- (N-CLEM: purity: 93.2%; EM 1251 + methylamin) carbonyl- (m / e): 374.52 (MH +, 100). methylenexyphenyl] -2,4- pñirnidindiamine? NMR (DMSO): d 8.71 (d, 1H, J = 4.5 Hz), 7.75 (s, 1H), N4- (3-Amino-l, 2.4- 7.53 (s, 2H), 7.21 (s, 1H) ), triazol-5-yl) -N2- (3.5-1252 6.61-6.74 (m, 2H), 5.83 (bs, dimethylphenyl) -5-fluoro-2H), 2.43 (s, 6H); LCMS: 2,4-? Irimidmdiamine purity: 88.8%; MS (m / e): 315.24 (MH +, 100). N4- (5-Amino-l, 2,4-triazole-3-y) -N2- (3-CLEM: purity: 92.8%; EM 1253 chloro-4-methoxyphenyl) -5- (m / e): 351.09 (MH +, 100). fluoro-2,4-pyrimidinediamine N4- (5-Amino-l, 2,4-triazol-3-yl) -N2- (3,4-CLEM: purity: 93.2%; EM 1254 dichlorophenyl) -5-fluoro- (m / e): 355.23 (MH +, 100). 2,4-? Irirm'dmdiamine N4- (5-Amino-l, 2,4-triazol-3-yl) -5-fluoro-CLEM: purity: 94.3%; MS 1255 N2- (indazol-6-yl) -2.4- (m / e): 327.14 (MH +, 100). + pyrimidinediamine No. Name of Compound Physical Data Tftasa Tftasa Tftasa f sik Com LD, ID, ID, Cpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt XH NMR (DMSO): d 10.09 (bs, 1H) , 9.12 (bs, 1H), 8.13 N4 - [(2,3-Dihydro-l, 4- (d, 1H, J = 5.1 Hz), 7.17 (s, benzodioxan-2H), 6.74-6.87 (m , 5H), 1256 yl) methyl] -N2- (3.5-4.29-4.50 (m, 2H), 3.98 (dd, + dimethylphenyl) -5-fluoro- 1H, 6.3, 11.4 Hz), 3.59-3.80 2 , 4-pyrimidinediamine (m, 2H), 2.23 (s, 6H); LCMS: purity: 97.8%; MS (m / e): 379.14 (M-, 100). N4 - [(2,3-Dihydro-l, 4-benzodioxan-2-yl) methyl] -5-fluoro-N2-LCMS: purity: 97.4%; MS 1257 [3- (N- + (m / e): 438.13 (M-, 100) methylamino) carboryl-methylenoxyphenyl] -2,4-pyrimidinediamine X H NMR (DMSO): d 10.13 (s, 1H), 9.05 (bs, 1H), 8.19 N4 - [(2,3-Dihydro-l, 4- (d, 1H, J = 4.8 Hz), 6.79-benzodioxan-2-6.86 (m, 6H), 6.24 (m, 1H ), il) methyl] -N2- (3.5-1258 4.29-4.49 (m, TH), 4.00 (dd, dimethoxyphenyl) -5- + 1H, 6.9, 11.4 Hz), 3.62-3.79 fluoro-2,4 - (m, 8H); LCMS: purity: pijrirm'dindiamine 96.7%; MS (m / e): 411.10 (M-, 100). T NMR (DMSO): d 10.22 (s, 1H), 9.11 (bs, 1H), 8.12 N2- (3-Chloro-4- (d, 1H, J = 5.1 Hz), 7.70 (d, methoxyphenyl) -N4 - [(2,3- 1H, J = 2.4 Hz), 7.35 (dd, dihydro-1,4- 1H, J = 2.7, 9.0 Hz), 7.08 (d, 1259 benzodioxan-2- 1H, J = 9.0 Hz ), 6.78-6.87 il) methyl] -5-fluoro-2,4- (m, 4H), 4.28-4.49 (m, 2H), pyrimidindiamine 3.99 (dd, 1H, 6.9, 11.7 Hz), 3.59-3.84 ( m, 5H); LCMS: purity N4 - [(2,3-Dihydro-l, 4-benzodioxan-2-LCMS: purity: 95.0%; EM 1260 il) methyl] -5-fluoro-N2- + (m / e): 391.10 ( M-, 100). (indazol-6-yl) -2,4-pyrimid dia ina N 4 - (3,4-Dichlorophenyl) -5-fluoro-N 2 - (4- CLEM: purity: 100%; EM 1261 methoxycarbonylphenyl) - (m / e ): 405.09 (M-, 100). 2,4-pyriridine diamine N2- [4- (N-Carboxymethyleneamino) LCMS: purity: 100%; EM 1262 carbomlfenu] -N4- (3,4- (m / e): 450.11 (M-) dichlorophenyl) -5-fluoro-2,4-? Irimidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com ID ID, ID, Cpt Lpt, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T XH NMR (DMSO): d 10.74 (s, 1H), 9.95 (s, 1H), 9.80 (s, (S ) -5-Fluoro-N2- (4-1H), 8.18 (d, lH, J = 4.2 Hz), methoxycarbonylphenyl) - 7.20-7.79 (m, 6H), 6.96 (d, N4- (2-methyl-3) -oxo- 1263 1H, J = 9.3Hz), 4.66 (q, 1H, 2H, 4H- J = 6.6 Hz), 3.78 (s, 3H), benz [1,4] oxazin-6-yl) - 1.45 ( d, 3H, J = 6.6 Hz); 2,4-pyrimidinediamine LCMS: purity: 96.8%; MS (m / e): 422.12 (M-, 100). T NMR (DMSO): d 10.75 (S) -N2- [4- (N- (s, 1H), 9.88 (s, 1H), 9.63 Carboxymethyleneamino) (m, 1H), 8.19 (d, lH, J = 4.5 carbonylphenyl] -5-fluoro-Hz), 7.19-7.75 (m, 6H), 6.98 1264 N4- (2-methyl-3-oxo- (d, 1H, J = 8.7Hz), 4.67 (q, 2H, 4H- 1H, J = 6.9 Hz), 3.89 (d, 1H, benz [1,4] oxazin-6-yl) - 5.7 Hz), 1.44 (d, 3H, J = 6.9, 2,4-pyridine, mdindiamine, Hz ); LCMS: purity: 91.2%; MS (m / e): 465.21 (M-, 100). (R) -N2- (4-Aminocarbonylphenyl) -5- fluoro-N4- (2-methyl-3-CLEM: purity: 95.5%; EM 1265 oxo-2H, 4H- (me): 407.17 (M-, 100 ). + benz [1,4] oxazin-6-yl) -2,4-pyrimidiadiamine XH NMR (DMSO): d 10.74 (s, 1H), 9.95 (s, 1H), 9.80 (s, (R) - 5-Fluoro-N2- (4-1H), 8.18 (d, lH, J = 4.2 Hz), methoxycarbonylphenyl) - 7.20-7.79 (m, 6H), 6.96 (d, N4- (2-methyl-3-oxo) - 1266 1H, J = 9.3Hz), 4.66 (q, 1H, + 2H, 4H- J = 6.6 Hz), 3.78 (s, 3H), benz [1,4] oxazin-6-yl) - 1.45 (d , 3H, J = 6.6 Hz); 2,4-pyriridinediamine LCMS: purity: 98.5%; MS (m / e): 422.17 (M-, 100). T NMR (DMSO): d 10.75 (R) -N2- [4- (N- (s, 1H), 9.88 (s, 1H), 9.63 Carboxymethyleneamino) (m, lH), 8.19 (d, lH, J = 4.5 carbonylphenyl] -5-fluoro-Hz), 7.19-7.75 (m, 6H), 6.98 1267 N4- (2-methyl-3-oxo- (d, 1H, J = 8.7Hz), 4.67 (q, 2H, 4H-1H, J = 6.9 Hz), 3.89 (d, 1H, benz [1,4] oxazin-6-yl) - 5.7 Hz), 1.44 (d, 3H, J = 6.9, 2,4-pyrimidinediamine Hz); LCMS: purity: 87.5%; MS (m / e): 465.21 (M-, 100). N2, N4-Bis [4- (N-tert-butoxycarbonarnino) LCMS: purity: 100%; EM 1268 + methylenephenyl] -5-fluoro- (m / e): 537.34 (M-, 100). 2,4-pyriptidin (namine No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, ID, ID, Cllpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO): d 9.25 (bs, 1H), 9.09 (bs, 1H), 8.05 (d, 1H, J = 2.4 Hz), 7.69 (d, N2, N4-Bis (4- 2H, J = 8.7Hz), 7.56 (d, 2H , aminomethylenephenyl) -5- 1269 J = 8.7 Hz), 7.04-7.40 (, + + fluoro-2,4- + 4H), 3.67 (s, 3H), 3.61 (s, pyrimidinediamine 3H), 3.35 (bs, 4H ); LCMS: purity: 95.5%; MS (m / e): 337.18 (M-, 100) T NMR (DMSO): d 10.21 (s, 2H), 8.33 (, 1H), 8.33 N4- (3.4 -Dichlorophenyl) - (d, 1H, J = 4.5 Hz), 8.10 (d, 5-fluoro-N2- [4- (N- 1H, J = 2.4 Hz), 7.59-7.83 1270 methoxycarbonylmethyl- (m, 6H) 3.99 (m, 2H), 3.65 enamino) carbonylphenyl] (s, 3H); LCMS: purity: -2,4-pyrimidmdiamine 100%; MS (m / e): 462.11 (M-, 100). X H NMR (DMSO): d 10.77 (S) -5-Fluoro-N 2 - [4- (s, 1 H), 9.93 (bs, 1 H), 8.77 (N- (m, 1 H), 8.20 (d, 1 H, J = 4.5 methoxycarbonylmethyl- Hz), 7.21-7.75 (m, 6H), 6.97 enamino) carbonylphenyl] (d, 1H, J = 8.4 Hz), 4.66 (q, 1271 + -N4- (2-methyl-3-oxo - 1H, J = 6.6 Hz), 3.97 (m, 2H, 4H-2H), 3.64 (s, 3H), 1.44 (d, benz [1,4] oxazin-6-yl) - 3H, J = 6.6 Hz ); LCMS: 2,4-pyrimidiamine purity: 96.7%; MS (m / e): 481.16 (MH +, Ti NMR (DMSO): d 10.77 (R) -5-Fluoro-N2- [4- (s, 1H), 9.93 (bs, 1H), 8.77 (N- ( m, 1H), 8.20 (d, 1H, J = 4.5 methoxycarbonylmethyl- Hz), 7.21-7.75 (m, 6H), 6.97 enamino) carbonylphenyl] (d, 1H, J = 8.4 Hz), 4.66 (q, 1272 - N4- (2-methyl-3-oxo- + 1H, J = 6.6 Hz), 3.97 (m, 2H, 4H-2H), 3.64 (s, 3H), 1.44 (d, benz [1,4] oxazin- 6-yl) -3 H, J = 6.6 Hz); LCMS: 2,4-pyrimidinediamine purity: 100%; MS (m / e): 481.39 (MH +,! H NMR (DMSO): d 9.43 (s, 1H) , 9.22 (s, 1H), 9.08 (d, 1H, J = 3.6 Hz), 7.24-7.72 N2, N4-Bis [3- (N-tert- (m, 7H), 7.15 (t, 1H, J = 7.8 butoxycarbonamino) 1273 Hz), 6.94 (d, lH, J = 7.5 Hz), + methylenephenyl] -5-fluoro-6.78 (d, 1H, J = 7.5 Hz), 4.08 2.4-pyrintidinediamine (m, 4H) , 1.39 (s, 18H); LCMS: purity: 95.8%; MS (m / e): 537.16 (M-, 100).

No. Name of Compound Physical Data Triptase Triptase Tftasa f sik Com LD, LD, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt lH NMR (DMSO): d 9.24 (s, N2, N4- Bis (3-1H), 8.35 (s, 1H), 8.01-8.07 aminometüenfenil) -5- (m, 2H), 6.73-7.71 (m, 7H), 1274 fluoro-2,4- 3.69 (s, 2H) 3.61 (s, 2H); + LCMS pimimidiamine: purity: 100%; MS (m e): 337.21 (M-, 100). N2- [3- (N-tert-Butoxycarbonylamino) LCMS: purity: 93.5%; EM 1275 methylenephenyl] -N 4 - (3,4- (m / e): 476.19 (M-, 100), dichlorophenyl) -5-fluoro-2,4-pyrimidinediamine T NMR (DMSO): d 10.61 (S) - N2- [3- (N-tert- (s, 1H), 9.30 (s, 1H), 9.04 (s, Butoxycarbonylamino) 1H), 8.03 (d, lH, J = 3.9 Hz), methylenephenyl] -5-fluoro - 7.22-7.54 (m, 5H), 7.10 (t, 1276 N4- (2-methyl-3-oxo- 1H, J = 7.5 Hz), 6.92 (d, 1H, + + 2H, 4H- J = 7.5 Hz ), 4.64 (q, 1H, J = benz [1,4] oxazin-6-yl) - 6.6 Hz), 4.01 (m, 2H), 1.44 2,4-pyrimidinediamine (d, 3H, J = 6.6 Hz) 1.39 (s, 9H); LCMS: purity: 95.1 TI NMR (DMSO): d 10.61 (s, 1H), 9.30 (s, 1H), 9.04 (s, (R) -N2- [3- (N-tert-1H), 8.03 (d , lH, J = 3.9 Hz), Butoxycarbonylamino) 7.22-7.54 (m, 5H), 7.10 (t, methylene-phenyl] -5-fluoro-1277 1H, J = 7.5 Hz), 6.92 (d, lH, + N4- ( 2-methyl-3-oxo- + J = 7.5 Hz), 4.64 (q, 1H, J = 2H, 4H- 6.6 Hz), 4.01 (m, 2H), 1.44 benz [l, 4] oxazin-6-yl ) (d, 3H, J = 6.6 Hz), 1.39 (s, 9H); LCMS: purity: 92.2 X H NMR (DMSO): d 9.60 N 2 - (3- (bs, 1 H), 9.31 (s, 1 H), 8.16 Aminomethylenephenyl) - (d, 1 H, J = 3.6 Hz), 8.12 (d, 1278 N4- (3,4-dichlorophenyl) -1H, J = 2.7 Hz), 6.81-7.88 5-fluoro-2,4- (m, 6H), 3.70 (s, 2H); pnimidindiamine CLEM: purity: 96.4%; MS (m / e): 376.11 (M-, 100). l NMR (DMSO): d 9.30 (s, (S) -N2- (3-1H), 9.08 (s, 1H), 8.05 (m, Aminomethylenephenyl) -5- 1H), 6.76-7.60 (m, 8H) , 4.63 fluoro-N4- (2-methyl-3 -1279 (q, 1H, J = 6.9 Hz), 3.64 (s, oxo-2H, 4H- + + 2H), 1.43 (d, 3H, J = 6.9 benz [1,4] oxazin-6-yl) - Hz); LCMS: purity: 100%; 2,4-pyrimidindiamine MS (m / e): 393.20 (M-, 100). X H NMR (DMSO): d 9.30 (s, (R) -N2- (3-1H), 9.08 (s, 1H), 8.05 (m, Aminomethylenefem) -5- 1H), 6.76-7.60 (m, 8H) , 4.63 fluoro-N4- (2-methyl-3-1280 (q, 1H, J = 6.9 Hz), 3.64 (s, + oxo-2H, 4H-2H), 1.43 (d, 3H, J = 6.9 benz [ 1, 4] oxazin-6-yl-Hz); LCMS: purity: 98.5%; 2,4-pyrimidimediamine MS (m / e): 393.20 (M-, 100).

No. Name of Compound Physical Data Triptase Tftase Triptase f sik Com ID, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt rH NMR (DMSO): d 10.69 (s, 1H), 10.18 (bs, 1H), 8.25 N4- (2,2-Dimethyl-3- (d, 1H, J = 4.5 Hz), 8.12-oxo-4H-8.17 (m, 2H), 7.73 (d, 1H, J 1281 benz [1,4] oxazin-6-yl) - = 8.1 Hz), 7.62 (d, 1H, J = + + 5-fluoro-N2- [3-7.5 Hz), 7.21-7.39 (m, m, ( oxazol-2-yl) phenyl] -2,4- 4 H), 6.76 (d, 1 H, J = 8.4 Hz), pj-rimidmdiamine 1.38 (s, 6H); LCMS: purity: 100%; MS (m / e): 445.14 (M-, 100). Tí NMR (DMSO): d 10.69 1282 + (s, 1H), 9.98 (bs, 2H), 8.22 (R) -5-Fluoro-N4- (2- (d, 1H, J = 2.4 Hz), 8.16 (m, methyl-3-oxo-2H, 4H-1H), 7.21-7.75 (m, 6H), 6.78 benz [1,4] oxazin-6-yl) -1283 (d, 1H, J = 8.4 Hz), 4.62 (q, + N2- [3- (oxazole-2-1H, J = 6.9 Hz), 1.42 (d, 3H, il) phenyl] -2.4- J = 6.9 Hz); LCMS: purity: pyrimid diamine 94.9%; MS (m / e): 431.15 (M-, 100). T NMR (DMSO): d 12.05 N4- (2,2-Difluoro-3- (s, 1H), 10.05 (s, 1H), 9.95 oxo-4H- (s, 1H), 8.27 (m, 1H), 8.25 benz [l, 4] oxazin-6-yl) - (d, 1H, J = 4.5 Hz), 8.14 (s, 1284 + + 5-fluoro-N2- [3-1H), 7.32-7.75 (m, 6H), 7.13 (oxazole-2-ü) phenyl] -2,4- (d, 1H, J = 9.0 Hz); LCMS: pyrimidinediamine purity: 98.0%; MS (m / e): 453.12 (M-, 100). N 4 - (4-Amino-3,4-dihydro-2 H -l- benzopyran-6-yl) -5- LCMS: purity: 87.8%; EM 1285 + fluoro-N2- [3- (oxazole- (m / e): 417.18 (M-, 100) .2-yl) phenyl] -2,4-pyrirnidinediamine T NMR (DMSO): d 10.71 N4- ( 2,2-Dimethyl-3- (s, 1H), 9.91 (bs, 1H), 8.73 oxo-4H- (m, 1H), 1.19 (d, 1H, J = 4.5 benz [1,4] oxazin-6 -il) - Hz), 7.19-7.74 (m, 6H), 6.94 1286 5-fluoro-N2- [4- (N- + + + (d, 1H, J = 8.4 Hz), 3.97 (m, methoxycarbonylmethyl- 2H), 3.64 (s, 3H), 1.38 (s, enarnino) carbonylphenyl] 6H); LCMS: purity: 97.5%; MS (m / e): 493.22 (M-, 100).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (4-N-tert-Butoxycarbonylamino- 3,4- dihydro-2H-l-CLEM: purity: 89.3%; EM 1287 benzopyran-6-yl) -5- (m / e): 517.26 (M-, 100). + fluoro-N2- [3- (oxazol-5-yl) phenyl] -2,4- pyrimidindiamine N4- (4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-I-CLEM: purity: 96.6%; EM 1288 benzopyran-6-yl) -5- (m / e): 516.90 (M-, 100). + + fluoro-N2- [4- (oxazol-5-yl) phenyl] -2,4- pyrimidinediamine N4- (4-N-tert-Butoxycarbomlamino-3,4-dihydro-2H-l-CLEM: purity: 87.2 %; EM 1289 benzopyran-6-yl) -5- (m / e): 517.54 (M-, 100). + fluoro-N2- [4- (oxazol-2-yl) phenyl] -2,4- pyrimidine diamine 5-Fluoro-N4- (4-hydroxy-3,4-dihydro-2H-1-benzopyran-6-) il) - LCMS: purity: 100%; MS 1290 N2- [4- (oxazole-5- (m / e): 518.16 (M-, 100). + Ü) phenyl] -2,4- p ntidmdiamine XH NMR (DMSO): d 10.40 (s, 1H ), 10.25 (s, 1H), 8.26 5-Fluoro-N4- (4- (d, 1H, J = 4.8 Hz), 8.15 (s, hydroxy-3, 4-dihydro-1H), 7.65-7.83 (m , 4H), 7.50 2H-l-benzopyran-6-yl) -1291 (d, 1H, J = 2.7 Hz), 7.40 (dd, N2- [4- (oxazole-2- + + ü) phenyl] -2 , 4-1H, J 2.7, 8.4 Hz), 7.32 (s, 1H), 6.81 (d, lH, J = 8.7 Hz), pmmidmdiamiiia 4.59 (t, 1H, J = 5.1 Hz), 4.20-4.24 (m, 2 H), 1.70-2.1 1 H NMR (DMSO-d 6): d 9.25 (s, 1 H), 9.19 (s, 1 H), (R, S) -N 4 - [4-Amino-8.35 (s, 1 H), 8.05 (d, J = 3.6 3,4-dihydro-2H-l-Hz, 1H), 7.99 (m, 1H), 7.20- benzopyran-6-yl] -5- 1292 7.63 (m, 5H), 6.62 (d , J = 8.7 + fluoro-N2- [3- (oxazole-Hz, 1H), 3.86-4.20 (m, 3H), 5-ü) phenyl] -2.4- 1.75-2.0 (m, 2H); LCMS: pijrintidmdiamine purity: 91.8%; MS (m / e): 419.3 (MH +).

No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, Cpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? T (R, S) -N4- [4-Amino- 3,4-dihydro-2H-l-benzopyran-6-yl] -5- LCMS: purity: 98.0%; EM 1293 fluoro-N2- [4- (oxazole- (m / e): 419.2 (MH +). 5-yl) phenyl] -2,4-pyrimidinediamine Q ^ S) -N4- [4-Amino-3,4 -dihydro-2H-l-benzopyran-6-yl] -5- LCMS: purity: 93.5%; EM 1294 fluoro-N2- [4- (oxazole- (me): 419.3 (MH +). + 2-ü) phenyl] -2,4-pyrimidinediamine 1H NMR (DMSO-d6): d N4- (2,2- Dimethyl-3- 10.73 (s, 1H), 9.97 (s, 1H), oxo-4H-9.87 (s, 1H), 8.53 (m, 1H), benz [1,4] oxazin-6-yl) - 8.19 (d, J = 4.2 Hz, 1H), 5-fluoro-N2- [4- [N- (N- 7.66-7.83 (m, 5H), 7.24-7.27 1295 + methylamino) carbonyl- (m, 2H), 6.94 (d, J = 8.4 Hz, + methylene] aminocarbonyl 1H), 3.78 (d, J = 5.7 Hz, 2H), -feml] -2.4- 2.58 (d, J = 4.5 Hz, 3H), 1.41 pyrimidinediamine (s, 6H); purity 98.2%; MS (m 1 H NMR (DMSO-d 6): d (S) -5-Fluoro-N 2 - [4- 10.85 (s, 1 H), 10.21 (s, 1 H), [N- (N- 9.98 (s, 1 H ), 8.58 (m, 1H), methylamino) carbonyl- 8.22 (d, J = 4.5 Hz, 1H), methylen] aminocarbonyl 7.68-7.79 (m, 6H), 7.43 (m, 1296 -feml) -N4- (2 -methyl-3-1H), 7.23 (m, 1H), 6.95 (d, J + oxo-2H, 4H- = 9.0 Hz, 1H), 4.65 (q, J = benz [1,4] oxazin-6 il) - 6.3 Hz, 1H), 3.79 (m, 2H), oxo-4H- 9.81 (s, 1H), 8.53 (m, 1H), benz [1,4] oxazin-6-yl) - 8.20 (d, J = 3.9 Hz, 1H), 5-fluoro-N2- [ 4- [N- (N- 7.67-7.78 (m, 6H), 7.54 (dd, 1297 methyamin) carbonyl- + J = 2.4, 8.7 Hz, 1H), 7.29 (d, methylene] aminocarbonyl J = 9.0 Hz, 1H ), 3.79 (d, J = -feml) -2.4- 6.0 Hz, TH), 2.58 (d, J = 4.2 pirii ^ diamine Hz, 1H); LCMS: purity: 97.8%; MS No. Compound Name Physical Data Triptase Triptase Tftasa f sik Com ID, ID, ID, Cpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt (R, S) -N4- [4- (N- ter-Butoxycarbon) amino-3,4-dihydro-2H-l- benzopyran-6-yl] -5- CLEM: purity 97% MS 1298 fluoro-N2- [4- [N- (N- (m / e) : 566.4 (MH +). + Methylamino) carbonyl-onyl (R, S) -N 4 - [4-Amino-3,4-dihydro-2 H -l- benzopyran-6-yl] -5- fluoro-N 2 - [4 - [N- (N-CLEM: purity: 93.5%; MS 1299 methylamin) carbonyl- (m / e): 466.3 (MH +). + + + metüen] aminocarbonyl-phenyl] -2,4-pyrimidyndiainine 1 H NMR (DMSO-d 6): d 9.84 (s, 1 H), 9.81 (s, 1 H), N 4 - (3,4-Dichlorophenyl) - 8.54 ( m, 1H), 8.24 (d, J = 3.9 5-fluoro-N2- [4- [N- (N-Hz, 1H), 8.10 (d, J = 2.4 Hz, methyamin) carbonyl- 1H), 7.68- 7.81 (m, 6H), 7.56 1300 methylene] aminocarboml (d, J = 9.0 Hz, 1H), 3.79 (d, J + + -phenyl] -2.4- = 6.0 Hz, TH), 2.58 (d, J = pyrimidinediamine 3.9 Hz, 3H); LCMS: purity: 100%; MS (m / e): 463.2 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (3,4-Dichlorophemethyl) - 9.75 (s, 1 H), 8.50 (m, 1 H), 5-fluoro-N 4 -methyl-N 2 - 8.12 (d, J = 4.8 Hz, 1H), [4- [N- (N- 7.63-7.79 (m, 7H), 7.34 (dd, 1301 methylanecarbonyl- J = 2.4, 9.6 Hz, 1H), 3.78 (d, + + methylene] aminocarbonyl J = 4.8 Hz, 2H), 3.09 (s, 3H), -phenyl] -2,4- 2.58 (d, J = 4.5 Hz, 3H), pyrimidimethamine CLEM: purity: 94.1%, MS (m / e): 477.2 (MH +). 1 H NMR (DMSO-d 6): d N 4 - (2,2-Dimethyl-3- 10.71 (s, 1 H), 9.93 (bs, TH), oxo-4 H-8.32 (m, 1 H), 8.19 (d, J = 4.8 benz [1,4] oxazin-6-yl) - Hz, 1H), 7.61-7.69 (m, 4H), 1302 5-fluoro-N2- [4- [N- (2- 7.22 -7.25 (, 2H), 6.94 (d, J + + + methoxycarbonylethyl) - = 6.93 Hz, 1H), 3.60 (s, 3H), aminocarbonyl] phenyl] - 3.44 (q, J = 6.9 Hz, 2H), 2.57 2,4-? Irj tidindiamine (t, J = 6.9 Hz, 2H), 1.41 (s, 6H); CLEM: purity: 97.5%; No. Name of Compound Physical Data Tftase Triptase Triptase f sik Com ID, ID, ID, CTCT, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d (S) -5- Fluoro-N2- [4- 10.83 (s, 1H), 10.32 (s, 1H), [N- (2-10.13 (s, 1H), 8.39 (m, 1H), methoxycarbonylethyl) - 8.25 (d, J • = 4.8 Hz, 1H), ammocarbonyl] phenyl] - 7.62-7.72 (m, 4H), 7.35 (s, 1303 + N4- (2-methyl-3-oxo-1H), 7.21 (dd, J = 2.4, 8.7 + 2H, 4H-Hz, 1H), 6.96 (d, J = 8.7 Hz, benz [1,4] oxazin-6-yl) - 1H), 4.66 (q, J = 6.9 Hz, 1H), 2.4 -piimidindiamine 3.59 (s, 3H), 3.43 (m, 2H), 2.57 1 H NMR (DMSO-d6): d 12.15 (s, 1H), 9.85 (m, 2H), N4- (2,2-Difluoro-3) - 8.31 (m, 1H), 8.20 (d, J = 4.2 oxo-4H-Hz, 1H), 7.70-7.78 (m, 5H), benz [1,4] oxazin-6-yl) - 7.50 (d, J = 9.6 Hz, 1H), 7.27 1304 5-fluoro-N2- [4- [N- (2- (d, J = 9.90 Hz, 1H), 3.59 (s, + methoxycarbonylethyl) -3H), 3.42 (m , 2H), 2.56 (t, J ammocarbonyl] phenyl] - = 6.9 Hz, 2H); LCMS: 2,4-pyrimidinediamine purity: 88.5%; MS (m / e): 517.3 (MH 1 H NMR (DMSO-d 6): d 9.82 (s, 1 H), 9.77 (s, 1 H), 8.36 (m, 1 H), 8.24 (d, J = 3.9 N 4 - ( 3,4-Dichlorophenyl) - Hz, 1H), 8.11 (d, J = 2.4 Hz, 5-fluoro-N2- [4- [N- (2-1H), 7.65-7.79 (m, 5H), 7.56 1305 methoxycarbonylethyl) - (d, J = 8.7 Hz, 1H), 3.60 (s, + + + aminocarbonyl] phenyl] - 3H), 3.47 (q, J = 6.6 Hz, 2H), 2,4-pyripidinediamine 2.57 ( t, J = 6.6 Hz, 1H), purity 90.9%, MS (m / e): 478 1H NMR (DMSO-d6): d 9.94 (s, 1H), 8.41 (m, 1H), N4- (3, 4-Dichlorophenyl) - 8.16 (d, J = 5.7 Hz, 1H), 5-fluoro-N2- [4- [N- (2- 7.64-7.75 (m, 6H), 7.36 (dd, methoxycarbonylethyl) - 1306 J = 2.4, 8.7 Hz, 1H), 3.59 (s, + + aminocarbonyl] phenyl] - 3H), 3.50 (s, 3H), 3.45 (m, N4-methyl-2,4-2H), 2.57 (t, J = 7.6 Hz, 2H); LCMS: purity: 88.5%; MS (m / e): 492.2 (MH +). 1H NMR (DMSO-d6): d N2- [4- [l- (tec- 10.59 (s, 1H), 9.29 (s, 1H), Butoxycarbonylamino) 9.01 (s, 1H), 8.12 (m, 1H), methylenecarbonylamino] 8.03 (d, J = 3.6 Hz, 1H), 7.56 methyphenyl] -N4- (2.2 - 1307 (d, J = 9.0 Hz, 2H), 7.27 (dd, tell me til-3-oxo-4H- + + J = 2.1, 8.4 Hz, 1H), 7.21 (d, benz [1,4] oxazin-6-yl) - J = 2.4 Hz, 1H), 7.05 (d, J = 5-fluoro-2,4- 8.7 Hz, 2H), 6.90 (d, J = 9.0 pyrirmdmdiamine Hz, 2H), 4.16 (d, J = 5.4 No. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt 1H NMR (DMSO-d6): d (S) -N2- [4- [l- (tert- 10.63 (s, 1H) , 9.29 (s, 1H), Butoxycarbonylamino) 9.00 (s, 1H), 8.13 (m, 1H), methylenecarbonylamino] 8.03 (d, J = 3.6 Hz, 1H), 7.29 methylphenyl] -5-fluoro-1308-7.57 ( m, 3H), 7.21 (d, J = + + + N4- (2-methyl-3-oxo- 2.1 Hz, 1H), 7.05 (d, J = 9.0 2H, 4H-Hz, 2H), 6.90 (d , J = 8.4 Hz, benz [1,4] oxazin-6-yl) -2H), 4.65 (q, J = 7.5 Hz, 1H), 2,4-pyrimidinediamine 4.16 (d, J = 5.7 Hz, 2H) 3 H NMR (DMSO-d 6): d N 2 - [4- [1 - (tert- 9.52 (s, 1H), 9.08 (s, 1H), Butoxycarbonylamino) 8.13 (m, 1H), 8.09 (d, J = 3.3 methylcarbomlamino] Hz, 1H), 7.46-7.62 (m, 4H), methylphenyl] -N4- (2.2-1309 7.23 (d, J = 8.7 Hz, 2H), 7.07 + + difl uoro-3 -OXO-4H- (d, J = 8.4 Hz, 2H), 6.92 (m, benz [1, 4] oxazin-6-yl) - 1H), 4.18 (d, J = 5.7 Hz, 2H) , 5-fluoro-2,4- 3.54 (d, J = 5.7 Hz, TH), 1.37 pyrimidinediamine (s, 9H); LCMS: purity: 93 1 H NMR (DMSO-d 6): d 9.56 (s, 1H), 9.28 (s, 1H), N2- [4- [l- (tert- 8.12-8.17 (m, 3H), 7.51- 7.81 Butoxycarbomlamino) (m, 4H), 7.14 (d, J = 8.7 Hz, methylenecarbonylamino] 1310 2H), 6.93 (m, 1H), 4.20 (d, J -f methylphenol) -N4- (3,4- + = 6.3 Hz, 2H), 3.54 (d, J = dichlorophenyl) -5-fluoro- 6.6 Hz, 2H), 1.38 (s, 9H); 2,4-pyrirm-mydiamine CLEM: purity: 94.1%; MS (m / e): 535.3 (MH +). 1 H NMR (DMSO-d 6): d 9.31 (s, 1 H), 8.15 (m, 1 H), N 2 - [4- [l- (tert- 8.04 (d, J = 5.4 Hz, 1 H), butoxycarbonylamino) 7.55- 7.66 (m, 4H), 7.30 (m, methylenecarbonylamino) 1H), 7.08 (d, J = 8.7 Hz, 2H), 1311 methylphenyl] -N4- (3.4-6.94 (m, 1H), 4.18 (d, J = 6.3 dichlorophenyl) -5-fluoro-Hz, 2H), 3.54 (d, J = 6.3 Hz, N4-methyl-2,4-2H), 3.46 (s, 3H), 1.38 (s, pm idindiamine 9H); LCMS: purity: 90.1%; MS (m / e N4- (2,2-Dimethyl-3-oxo-4H-5-CLEM: ret. Time: 3.67 pyrid [1,4] oxazin-6-yl) - min. (9 min. Method); 1312 5-fluoro-N2- [4- [N- (2-purity: 95.3%; MS (m / e): + methoxycarbonylethyl) -496.3 (MH-r). Aminocarbonyl] phenyl] -2,4-pyrimidinediamine N4- (2,2-Dimethyl-3-oxo-4H-5- CLEM: ret time: 4.45 pyrid [1,4] oxazin-6-yl) - min. (9 min. Method): 1313 + 5-fluoro -N2- (4- purity: 97.3%; MS (m / e): methoxycarbonyl phen) - 439.3 (MH +). 2,4-pyrimidinediamine No. Compound Name Physical Data Triptase Tftase Tftasa f sik Com ID, ID, LD, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (2,2-Dimethyl-3-oxo-4H-5-CLEM: Ret. time: 4.00 pyridfl, 4] oxazin-6-yl) - min. (9 min method): 1314 5-fluoro-N2- (3- purity: 95.1%; MS (m / e): methoxycarbonylpyrid-2- 440.4 (MH +). ü) -2,4-pyrylimidiamine N2 - (4- Aminocarbonylphenyl) - CLEM: Ret. Time: 3.28 N4- (2,2-dimethyl-3-oxoamia. (9 min. Method); 1315 4H-5-? Irid [1,4] oxazin- purity: 98.1%; MS (m / e): 6-yl) -5-fluoro-2,4- 424.3 (MH +). idindiamine N2- (2-Aminocarbonylphenyl) - CLEM: Ret. time: 3.98 N4- (2,2-dimethyl-3-oxo-min. (9 min method); 1316 + 4H-5-pyrid [1,4] oxazin-purity: 90.1%; MS (m / e): 6-yl) -5-fluoro-2,4- 424.5 (MH +). pyripiidinediamine Methane sulfonic acid salt of N4-LCMS: retin time: 8.50 (2,2-Dimethyl-3-oxo-min. (20 min. method); 1317 4H-benz [1,4] oxazin-6- purity: 98.8%; MS (m / e): il) -5-fluoro-N2- 420.1 (MH +). (indazol-6-yl) -2,4-pyrimidinediamine N4- (2,2-Difluoro-3-oxo-CLEM methanesulfonic acid salt: time ret .: 9.69 4H-benz [1,4] oxazin-6- min (20 min method): 1318 ü) -5-fluoro-N2- [3- (N- purity: 98.4%; MS (m / e): methyla) carbonyl- 475.3 (MH +). methylenexyphenyl] -2,4- pyrimidinediamine N 4 - (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: retentate time: 3.17 N 2 - (4- [N- [methoxymine (7 min. 1319 carbonylmethylene] amino purity: 97.5%; MS (m / e): + carbonyl] phenyl) -2.4- 460.3 (MH +). pyruididinediamine N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret. time: 2.64 N2- (4- [2- [N, N- min. (7 min. method); 1320 diethylamino] ethylene - purity: 100%; MS (m / e): aminocarbonyl] phenyl) -487.3 (MH +). 2,4-pyrimidindiamine No. Name of Compound Physical Data Triptase Triptase Tftasa f_sik Com ID, ID, ID, Cpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- (4- CLEM: Ret Time: 2.86 Aminocarbonylphenyl) - min. (7 min method); 1321 N4- (3-chloro-4- purity: 100%; MS (m / e): + + methoxyphenyl) -5-fluoro-488.3 (MH +). 2,4-p? Imidindiamine N4- (3-Chloro-4- CLEM: time ret: 4.02 methoxyphenyl) -5-fluoro- min. (7 min method); 1322 N2- (4- purity: 98.4%; MS (m / e): + methoxycarbonylphenyl) - 403.3 (MH +). 2,4-pyrimidindiamine N 4 - (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret time: 3.83 N 2 - (4- [N-tert.-min. (7 min. Method); 1323 butoxycarbonyl- purity : 92.3%; MS (m / e): + aminomethylene] phenyl) - 474.3 (MH +). 2,4-pyridine-idindiamine N2- (4- CLEM: time ret: 2.53 Aminomethylenephenyl) - min. (7 min method); 1324 N4- (3-chloro-4- purity: 96.6%; MS (m / e): + methoxyphenyl) -5-fluoro-2,4-ptrimidindiamine 374.2 (MH +). N4- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: time ret .: 2.81 N2- (4- [N- [N- min. (7 min. Method); 1325 methyl] aminocarbom- purity: 100%; MS (m / e): metüen] amino-459.3 (MH +). Carbonyl] phenyl) -2,4-pyrimidimediamine 2-Chloro-5-fluoro-N4-CLEM: time ret .: 2.79 (4- [ N- [methoxycarbonylmin (7 min methylene] amino-method); 1326 purity: 100%; MS (m / e): carbonyl] phenyl) -4- 339.2 (MH +). pyrimidinamine N4- [4- CLEM: ret time: 2.40 Ammocarbonylphenyl] -2- min. (7 min method); 1327 chloro-5-fluoro ~ 4- purity: 100%; MS (m / e): pyrimid amine 267! (MH +). 5-Fluoro-N2- (3-hydroxyphenyl) -N4- (4-CLEM: ret. Time: 2.44 [N- [methoxycarbomethyl] (7 min method); 1328 methylene] amino-purity: 94.9%; (m / e): + carbonyl] phenyl) -2.4- 412.3 (MH +). pyrip.dindiamine N2- (3,5-Dichloro-4-hydroxyphenyl) -5-fluoro-CLEM: time ret .: 9.92 N4- (4- [N- min. (20 min. method); 1329 [methoxycarbonyl- purity 95.0%; MS (m / e): + methylene] amino- 482.0 (MH +). Carbonyl] phenyl) -2,4- pyrimidinedia Nay. Compound Name Physical Data Triptase Triptase Triptase f sik Com ID, ID, ID , llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3? t N2- (3-Chloro-4-methoxyphenyl) -5-fluoro-CLEM: ret time: 3.13 N4- (4- [N- [ methoxyim (7 min method); 1330 + carbonylmethylene] amino purity: 95% MS (m / e): + carbonyl] phenyl) -2.4- 460.3 (MH +). pyrimidinediamine N2- (2,2-Dimethyl-3-oxo-4H-benz [1,4] oxazin-6-yl) - CLEM: ret time: 2.80 5-fluoro-N4- (4- [N-min. 7 min method); 1331 + [methoxycarbonyl- purity: 92.2%; MS (m / e): 495.3 (MH +) .5-Fluoro-N2, N4-bis (4- CLEM: ret time: 2.77 [N- [ methoxycarbomethyl (7 min method), 1332 metüen] amino- + purity: 100%, MS (m / e): carbonyl] phenyl) -2,4- 511.4 (MH +). pyrimidinediamine N 2 - (4-aminocarbonylphenyl) ) -5 - CLEM: time ret .: 2.48 fluoro-N4- (4- [N- min. (7 min method); 1333 [methoxycarbonyl- purity: 97.6%; MS (m / e): methylene] amino- 439.3 (MH +). Carbonyl] phenyl) -2,4-pyrimidinediamine N4- (4-Aminocarbonyl-CLEM: ret time: 2.10 phenyl) -5-fluoro-N2- (3- min. (7 min. Method): 1334 + hydroxyphenyl) -2,4- purity: 100%; MS (m / e): pyrin? dmdiamine 340.2 (MH +). N4- (4-Aminocarbonyl-CLEM: ret. time: 8.72 phenyl) -N2- (3, 5-dichloromin (20 min method); 1335 4-hydroxyphenyl) -5- + purity: 93.0%; MS (m / e): fluoro-2,4-410.0 (MH +). pijrimidindiamine N4- (4-Aminocarbonyl-CLEM: time ret .: 2.79 feml) -N2- (3-chloro-4- min. (7 min method); 1336 + methoxyphenyl) -5-fluoro-purity: 100%; MS (m / e): + N4- (4-Aminocarbonifenyl) -N2- (2,2-dimethyl-LCMS: time ret .: 2.50 3-oxo-4H-min. (7 min. Method); benz [1,4] oxazin-6-yl) - purity: 100%; EM (m / e): + -fluoro-2,4- 423.3 (MH +). pyrj tidmdiamine No. Compound Name Physical Data Triptase Triptase Triptase f sik Com LD, LD, ID, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (Aminocarbonylphenyl) - CLEM: Ret Time: 2.52 5 -fluoro-N2- (4- [N- min. (7 min method); 1338 [methoxycarbonyl- purity: 94.4%; MS (m / e): + methylene] amino- 439.3 (MH +). carbonyl] phenyl) -2,4- pyrimidinediamine N2, N4-Bis (4- CLEM: ret time: 2.26 ammocarbonylphenyl) -5- min. (7 min method); 1339 fluoro-2,4-purity: 100%; MS (m / e): pyrimidinediamine 367.3 (MH +). N4- (2,2-Dimethyl-3-oxo-4H-N4-oxo-5-CLEM: ret. Time: 3.48 pyrido [1,4] oxazin-6-yl) -min. (7 min method); 1340 5-fluoro-N2- (3.4.5- purity: 97.4%; MS (m / e): + trimethoxyphenyl) -2.4-487.3 (MH +). piirirm ^ indiamina CLEM: ret time: 2.72 [3-methyl-l, 2,4-min. (7 min method); 1341 oxadiazole-5 purity: 95.8%; MS (m / e): + + + il] methyleneoxyphenyl) -2.4-43.6.3 (MH +). pyridinediamine 5-Fluoro-N2- (4- [N- [methoxycarbonyl-methylene] amino-LCMS: ret time: 2.99 carbonyl] phenyl) -N4- (4 min. (7 min. method); 1342 [3- methyl-l, 2,4-purity: 95.1%; MS (m / e): + oxadiazole-5-508.4 (MH +). il] methylenexypheni) -2,4- pyrirm ^ indiamine N2- (4- [2- [N, N-Diethylamino] ethylene-CLEM: ret time: 2.58 aminocarbortyl] phenyl) -min. (7 min method); 1343 5-fluoro-N4- (4- [3- purity: 97.8%; MS (m / e): + + + methyl-1,2,4-oxadiazole-535.4 (MH +). 5-ü] methyleneoxyphenyl) - 2,4-pirirm ^ india? Nina N2- (3,5-Dichloro-4-hydroxyphenyl) -5-fluoro-CLEM: ret. Time: 3.33 N4- (4- [3-methyl-l, 2,4- min. (7 min. method); 1344 oxadiazole-5 purity: 95.0%; MS (m / e): + + il] methylenexyphenyl) -2.4-47.7.2 (MH +). pyrirm ^ indiamine N2- (3-Chloro-5-methoxyphenyl) -5-fluoro-CLEM: ret time: 3.35 N4- (4- [3-methyl-1, 2.4-min. (7 min. method); 1345 oxadiazole-5- purity: 96.4%; MS (m / e): + il] methylenexyphenyl) -2.4-457.3 (MH +). primidindiamine No. Name of Compound Physical Data Triptase Triptase Triptase f sik Com LD, ID, ID, llpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N2- (4- CLEM: Ret. time: 3.86 Aminocarbonylphenyl) - min. (7 min method); 1346 N 4 - (3,4-dichlorophenyl) - purity: 100%; MS (m / e): 5-fluoro-N 4 -methyl-2,4-406.2 (MH +). pyrimidiammine N2- (4- [2- [N, N-Diethylamino] ethylene-CLEM: ret. time: 3.31 aminocarboml] phenyl) -min. (7 min method); 1347 + N4- (3,4-dichlorophenyl) - purity: 100%; MS (m / e): 5-fluoro-N 4 -methyl-2,4- 505.3 (MH +). pyrimidinediamine N4- (3,4-Dichlorophenyl) -5-fluoro-N2- (4- [N-CLEM: time ret: 4.16 [methoxycarbonylmin. (7 min. method); 1348 methylenejamino- + purity: 95.8%; MS (m / e): carbonyl] phenyl) -N 4 - 480.2 (MH +). methyl-2,4-pyrimimidineamine LCMS: time ret .: 2.26 Aminocarbonylphenyl) -min. (7 min method); 1349 N4- (cyclopentyl) -5- purity: 100%; MS (m / e): fluoro-2,4- 316.3 (MH +). pdyldindiamine N4- (Cyclopentyl) -N2- (4- [2- (N, N-CLEM: time ret .: 2.09 dietamino] ethylene (7 min method) 1350 aminocarbonyl) phenyl) - purity: 97.3%; MS (m / e): + 5-fluoro-2,4-415.4 (MH +). N4- (Cyclopentyl) -5- fluoro-N2- (4- [N-CLEM: ret time: 2.62 [methoxycarbonylmin. (7 min method); 1351 + + methylene] amino purity: 100%; m / e): carbonyl] phenyl) -2.4-388.3 (MH +). n-N-diamine N2- (4-Aminocarbonyl-LCMS: ret time: 3.13 phenyl) -N4- (4-chloro-3-min. (7 min method); 1352 methoxyphenyl) -5-fluoro-purity: 96.4%; MS (m / e): + 2,4-pyrimidinediamine 388.3 (MH +). N2- (4-aminocarbonyl-LCMS: ret time: 2.91 3-chlorophenyl) -N4- (3- min. (7 min. Method); 1353 chloro-4-methoxyphenyl) -5- purity: 89.5%; MS (m / e): + fluoro-2,4- 422.2 (MH +). pyrimidinediamine N2- (4-Aminocarbonyl-LCMS: ret time: 3.14 3-chlorophenyl) -N4- (4 min. (7 min. method); 1354 chloro-3-methoxyphenyl) -5- + purity: 95.0%; MS (m / e): fluoro-2,4-242.2 (MH +). pyrimidindiamine No. Name of Compound Physical Data Triptase Tftase Triptase f_sik Com ID, ID, LD, Lpt CMC, CMC, CMC, IgE, 3pt IgE, 8pt Ion, 3pt N4- (4-Chloro-3-methoxyphenyl) -N2- ( 4- [2- LCMS: time ret: 2.80 [N, N-diethylamino] -min. (7 min method); 1355 etüenaminocarbonyl] - purity: 95.6%; MS (m / e): + + phenyl) -5 -fluoro-2,4-487.4 (MH +). pindinindiamine N4- (4-Chloro-3-methoxyphenyl) -5-fluoro-CLEM: time ret .: 3.45 N2- (4- [N- [methoxyim.] (7 min.; 1356 carbonijtaethylene] amino purity: 94.6%; MS (m / e): + carbonyl] phenyl) -2.4- 460.3 (MH +). pminidinediamine N2- (4-Aminocarbonyl-CLEM: ret. time: 2.58 phenyl) -5-fluoro-N4- min. (7 min method); 1357 + phenyl-2,4-purity: 100%; MS (m / e): + pyridine diamine 424.3 (MH +). Hydrochloric acid salt of 5- LCMS: Ret time: 2.72 Fluoro-N2- (3- min. (7 min method); 1358 hydroxyphenyl) -N4- (4- [3- purity: 89.9%; EM (m / e): methyl-l, 2,4-oxadiazole-409.3 (MH +). 5-yl] methyleneoxyphenyl) -2,4-pi rimidinediamine The Compounds are Effective for the Treatment of Autoimmunity The in vivo efficacy of certain 2,4-pyrimidinediamine compounds towards autoimmune diseases was evaluated in the reverse passive Arthus reaction, an acute model of tissue injury mediated by antigen-antibody, and in several models of autoimmunity and inflammation diseases. These models are similar in that the antibody to a specific antigen mediates the inflammatory diseases activated by immune complexes (activated by IC) and destroys the subsequent tissue. IC deposition at specific anatomical sites (central nervous system (CNS) for experimental autoimmune encephalomyelitis (EAE) and synovium for collagen-induced arthritis (CIA)), leads to the activation of cells expressing FceR and Fc? R on the surface, notably mast cells, macrophages and neutrophils, which result in the release of cytokine and neutrophil chemotaxis. The activation of the inflammatory response is responsible for the downstream effector responses, which include edema, hemorrhage, neutrophil infiltration and release of pro-inflammatory mediators. The consequences of these events activated by HF are difficult to identify in autoimmune disorders; however, many researchers have shown that the inhibition of the FcγR signaling pathway in these animal models has resulted in a significant reduction in the onset and severity of the disease.

The Compounds are Effective in the Arthus Reaction in Mice The in vivo efficacy of compounds 810, 944, 994 and 1007, to inhibit the IC-induced inflammatory cascade, was demonstrated in a mouse model of the Reverse Passive Arthus Reaction (reaction RPA).

Model Inflammatory tissue injury mediated by the immune complex (IC) is implicated in a variety of human autoimmune diseases, including vasculitis syndrome, serum sickle cell disease, systemic lupus erythematosus (SLE), rheumatoid arthritis, Good Shepherd and glomerulonephritis. The classical experimental model for IC-mediated tissue injury is the reverse passive Arthus reaction. The RPA reaction model is a convenient in vivo method for studying localized inflammation, induced by IC, without systemic effects. Intradermal injection of antibodies (Abs) specific to chicken egg albumin (rabbit anti-OVA IgG), followed by intravenous (IV) injection of antigens (Ags), specifically chicken egg albumin (ovalbumin, OVA), causes perivascular deposition of HF and a rapid inflammatory response, characterized by edema, neutrophil inflammation and hemorrhages at injection sites. Aspects of the mouse RPA reaction model, resemble the inflammatory response of patients with rheumatoid arthritis, SLE and glomerulonephritis.

Study Protocol In this model system, the test compounds are administered at several time points prior to the administration of Abs and Ags. A solution of rabbit anti-OVA IgG (50 μg in 25 μl / mouse) is injected intradermally, and immediately afterwards there is an intravenous injection of chicken egg albumin (20 mg / kg body weight) into a solution that contains 1% Evans blue dye. The degree of edema and hemorrhage is measured in the dorsal skin of C57BL / 6 mice, using the Evans Blue dye as an indicator of local tissue damage. The purified polyclonal rabbit IgG is used as a control. The pre-treatment time in which the test compounds are administered prior to the Ab / Ag change, depends on the pharmacokinetic (PK) properties of each individual compound. Four hours after the induction of the Arthus reaction, the mice are euthanized and the tissues are harvested for evaluation of the edema. This model system allows to quickly select the in vivo activity of many inhibitors.

Results All test compounds were administered by the oral route. Compound 994, when administered at a dose level of 100 mg / kg 90 minutes prior to Ab / Ag change in C57B16 mice, showed dose-dependent inhibition of edema formation (75%). Compounds 1007 and 810 showed the efficacy of edema inhibition by 89.4% and 81.3%, respectively, when administered at 1.0 mg / kg, 30 minutes prior to the change. Compound 1007 showed 64.3%, 78.7%, 98.1% and 99. 8% inhibition of edema formation, when administered at dose levels of 0.1 mg / kg, 0.5 mg / kg, 1.0 mg / kg and 5 mg / kg and at a pretreatment time of 30, respectively. The results for the compounds tested are summarized in Table 2.

Table 2 Compounds are Effective in Arthritis Model Induced by Mouse Collagen Antibody The in vivo efficacy of compounds towards autoimmune diseases can be demonstrated in a mouse model of arthritis induced by collagen antibody (CAIA).

Model Collagen-induced arthritis (CIA) in rodents is frequently used as one of the experimental models for IC-mediated tissue injury. The administration of Type II collagen in mice or rats results in an immune reaction that characteristically involves the inflammatory destruction of cartilage and bone of the distal joints, with concomitant swelling of the surrounding tissues. The CIA is commonly used to evaluate compounds that could be of potential use as drugs, for the treatment of rheumatoid arthritis and other chronic inflammatory conditions. In recent years, a new technique has emerged in CIA modeling, in which anti-type II collagen antibodies are applied to induce an antibody-mediated CIA. The advantages of the method are: short time for induction of the disease (which develops within 24-48 hours after an intravenous (IV) injection of antibodies); arthritis is inducible in both CIA-resistant mouse strains as CIA-inducible; and the procedure is ideal for the rapid selection of anti-inflammatory therapeutic agents. The monoclonal antibody cocktail that induces Arthrogen-CIA® arthritis (Chemicon International Inc.), is administered intravenously to Balb / c mice (2 mg / mouse) at Day 0. Forty-eight hours later, 100 μl of LPS (25 μg) ), are injected intraperitoneally. By day 4, the toes may appear swollen. On day 5, one or two legs (particularly the hind legs), they start to look red and swollen. On day 6 and later, the red and swollen legs will remain for at least 1-2 weeks. During the study, clinical signs of inflammation are recorded to assess the intensity of foot edema. The severity of arthritis is recorded as the sum of the registration of both hind legs for each animal (maximum possible record of 8). The degree of inflammation which involves the legs is evaluated by measuring the diameter of the legs. Changes in body weight. Animals can be treated at the time of arthritis induction, beginning at day 0. Test compounds and control compounds can be administered once daily (qd) or twice a day (bid), per os (PO), depending on the previously established PK profiles. At the end of the study (1-2 weeks after the induction of arthritis), the mice are euthanized and the legs are transected in the distal tibia using a guillotine and weighed. The mean + the standard error (SEM) for each group is determined each day from the individual clinical records of the animal, and the weights of the hind legs for each experimental group are calculated and recorded at the end of the study. The histopathological evaluation of the legs is obtained.

Results Inflammation and reduced swelling should be evident in animals treated with compounds of the invention, and arthritis could progress more slowly. Treatment with the compounds should (b.i.d.) significantly reduce clinical arthritis compared to animals treated with vehicle alone.

The Compounds May Be Effective in Collagen-Induced Arthritis in Rats The in vivo efficacy of the compounds of the invention towards autoimmune diseases can be demonstrated in a rat model of collagen-induced arthritis (CIA).

Description of the Model Rheumatoid arthritis (RA) is characterized by chronic inflammation of joints, eventually leading to irreversible cartilage destruction. IC that contains IgG is abundant in the synovial tissue of patients with RA. While it is still debated what functions these complexes play in the etiology and pathology of the diseases, the CI communicates with the hematopoietic cells via the Fc? R. The CIA is a widely accepted animal model of RA that results in chronic inflammatory synovitis, characterized by formation of vascular keratitis and joint degradation. In this model, intradermal immunization with native type II collagen, emulsified with incomplete Freund's adjuvant, results in an inflammatory polyarthritis within 10 or 11 days and subsequent destruction of the joints in 3 to 4 weeks.

Study Protocol Synthetic LOU rats were immunized at day 0 with native chicken CII / IFA (performed at UCLA, E. Brahn, Principal Investigator). Beginning on the day of the onset of arthritis (Day 10), a total of 59 rats may be treated with either a control vehicle or a compound of the invention at one of four dose levels (1, 3, 10 and 30 mg. / kg, qd for forced feeding).

Results The hind limbs could be recorded daily to determine the severity of clinical arthritis using a standardized method based on the degree of inflammation of the joints. High-resolution digital radiographs of the hind limbs can be obtained at the conclusion of the study (Day 28). These extremities can also be analyzed to determine histopathological changes. IgG antibodies to native CII can be measured in quadruplicate by ELISA. Although the aforementioned invention has been described in some detail to facilitate understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims. Accordingly, the embodiments described are to be considered as illustrative and not restrictive, and the invention is not limited to the details given in this document, but may be modified within the scope and equivalents of the appended claims. All literature and patent references cited through the application are incorporated by reference in the application for all purposes.

Claims (50)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A 2,4-pyrimidinediamine compound according to structure (I): characterized in that it includes salts, hydrates, solvates and N-oxides thereof, wherein: L1 is a direct bond or a linker; L2 is a direct link or a linker; X is selected from the group consisting of N and CH; And it is selected from the group consisting of 0, S, SQ, S02, SONR36, NH, NR35 and NR37. Z is selected from the group consisting of O, S, SO, S02, SONR36, NH, NR35 and NR37; R5 are selected from the group consisting of R6, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C1-C4) alkanyl optionally substituted with one or more of the same or different R8 groups, (C2-C4) alkenyl optionally substituted with one or more of the same or different R8 groups and (C2-C4) alkynyl optionally substituted with one or more of the same or different R8 groups; each Rd is independently selected from the group consisting of hydrogen, an electronegative group, ~ 0Rd, -SRd, haloalkyloxy (C1-C3), perhaloalkyloxy (C1-C3), -NRCRC, halogen, haloalkyl (C1-C3), perhaloalkyl ( C1-C3), -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, -N3, -S (0) Rd, -S (0) 2Rd, - S (0) 20Rd, -S (0) NRcRc, -S (0) 2NRcRc, -OS (0) Rd, -0S (02) Rd, -0S (0) 20Rd, -0S (0) NRcRc, - 0S (0) 2NRcRc, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc, -C (NH) NRCRC, -0C (0) Rd, -SC (0) R, -0C ( 0) 0Rd, -SC (0) 0Rd, -0C (0) NRcRc, -SC (0) NRcRc, -OC (NH) NRCRC, -SC (NH) NRCRC, - [NHC (0)] pRd, - [ NHC (0)] p0Rd, - [NHC (0)] nNRcRc and - [NHC (NH)] pNRcRc, aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, aryl (C6-C16) optionally substituted with one or more of the same or different R8 groups, 5-10 element heteroaryl optionally substituted with one or more thereof or different is R8 groups and heteroarylalkyl of 6-16 elements optionally substituted with one or more of the same or different R8 groups; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or Rb, -B (0Ra) 2, -B (NRCRC) 2, - (CE2) m-Rb, - (CHRa) m-Rb, -0- (CH2) m-Rb, S- (CR2) m-Rb, 0-CHRaRb, -0-CRa (Rb) 2, -O- (CHRa) m -Rb -0- (CH2) JH-CH [(CH2) J! Rb] Rb, -S- (CHRa) m -Rb, -C (O) NH- (CH2) m -Rb, -CYOJ H-ÍCHR ^ -R13, -0- (CH2) ffl-C (0) NH- (CH2) m-Rb, -S- (CH2) ffl-C (0) NH- (CH2)? I-Rb, -O- (CHRa) ffl-C (0) NH- (CHRa) m-Rb, -S- (CHRa)? -C (0) NH- (CHRa) ffl-Rb, -NH- (CH2) ^ -R13, -NH- (CHRa) a-Rb , NH [(CH2) pRB], - UCH ^ R ^ s, -NH-C (O) -NH- (CH2) m -Rb, -NH-C (O) - (CH2) ffl-CHRRb and -NH- (CH2) aC (0) -NH- (CH2) m-Rb; each R31, independently of the others, is methyl or (C1-C6) alkyl; each R35 is, independently of the others, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 are each, independently of each other, selected from the group consisting of hydrogen and R8; each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl; each R37 is independently selected from the group consisting of hydrogen and a progroup; R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -0S (0) 2Rd, -OS (0) 2ORd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (N0H) Ra, -C (N0H) NRcRc, -0C (0) Rd, -0C (0) 0Rd, - 0C (0) NRcRc; 0C (NH) NRcRc, -0C (NRa) NRcRc, - [NHC (O)] nRd, - [NRaC (O)] pRd, - [NHC (O)] pOR, ~ [NRaC (0)] pORd, - [NHC (0)] pNRcRc, - [NRaC (O)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] nNRcRc; each Rc is independently a protecting group or Ra, alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more thereof or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently a protective group or Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3. yy is 1 to 6.

2. The compound according to claim 1, characterized in that R5 is fluoro.

3. The compound according to claim 2, characterized in that R6 is hydrogen.

4. The compound according to claim 1, characterized in that Y and Z are each, independently of each other, selected from the group consisting of O and NH.

5. The compound according to claim 4, characterized in that X is CH.

6. The compound according to claim 5, characterized in that Y and Z are each O.

7. The compound according to claim 6, characterized in that each R35 is hydrogen.

8. The compound according to claim 5, characterized in that Y is O and Z is NH.

9. A 2,4-pyrimidinediamine compound according to the structure: characterized in that it includes salts, hydrates, solvates and N-oxides thereof, wherein: L1 is a direct bond or a linker; L2 is a direct link or a linker; R2 is a phenyl group disubstituted with two groups Rb or R2 is a trisubstituted phenyl group with three Rb groups; X is selected from the group consisting of N and CH; And it is selected from the group consisting of O, S, SO, S02, SONR36, NH, NR35 and NR37; Z is selected from the group consisting of 0, S, SO, S02, SONR36, NH, NR35 and NR37; R5 are selected from the group consisting of R6, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C1-C4) alkanyl optionally substituted with one or more of the same or different R8 groups, (C2-C4) alkenyl optionally substituted with one or more of the same or different R8 groups and (C2-C4) alkynyl optionally substituted with one or more of the same or different R8 groups; each R6 is independently selected from the group consisting of hydrogen, an electronegative group, -0Rd, -SRd, haloalkyloxy (C1-C3), perhaloalkyloxy (C1-C3), -NRCRC, halogen, haloalkyl (C1-C3), perhaloalkyl ( C1-C3), -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, ~ N3, -S (0) Rd, -S (0) 2Rd, - S (0) 20Rd, -S (0) NRcRc, -S (0) 2NRcRc, -0S (0) Rd, -0S (02) Rd, -0S (0) 20Rd, -OS (0) NRcRc, - OS (0) 2NRcRc, -C (0) Rd, -C (0) ORd, -C (0) NRcRc, -C (NH) NRCRC, -0C (0) Rd, -SC (0) Rd, -OC ( 0) ORd, -SC (0) ORd, -0C (0) NRcRc, -SC (0) NRcRc, -OC (NH) NRCRC, -SC (NH) NRCRC, - [NHC (O)] ORd, - [ NHC (0)] n0Rd, - [NHC (0)] nNRcRc and - [NHC (NH)] pNRcRc, aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different groups R8, arylalkyl (C6-C16) optionally substituted with one or more of the same or different groups R8, heteroaryl of 5-10 elements optionally substituted with one or more thereof or different the R8 groups and 6-16-membered heteroarylalkyl optionally substituted with one or more of the same or different R8 groups; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different R or Rb, -ORa substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH2) m-Rb, - (CHRa) ffl-R, -O- (CH2) m ~ Rh, -S-ÍCH ^ -R13, 0-CHRaRb, -0-CRa ( Rb) 2, -O- (CHRa) m-Rb -0- (CE2) mC [(CH2)? NRb] - Rb, -S- (CHRa) m -Rb, -C (O) NH- (CH2) m-Rb, C (0) NH- (CHRa) ra-Rb, -0- (CH2)? nC (0) NH- (CH2) ffi-Rb, -S- (CH2) m- C (0) NH - (CH2) a? -Rb, -0- (CRRa) mC (0) Nñ- (CHRa) m -Rb, -S- (CHRa) mC (0) NH- (CHRa)? -Rb, -NH- (CH2) ^ -R13, -NH- (CHRa) m-Rb, NH [(CH2) ffiRb], - N [(CH2) JBRb] 2 / -NH-C (O) -NH- (CH2) m -Rb, -NH-C ( O) - (CH2)?! - CHRbRb and -NH- (CH2) mC (O) -NH- (CH2) rn- ^, each R35 is, independently of the other s, selected from the group consisting of hydrogen and R8 , or, alternatively, two R 5s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 are each, independently of each other, selected from the group consisting of of hydrogen and R8; each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl; each R37 is independently selected from the group consisting of hydrogen and a progroup; R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -ORd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc , -S (0) 2NRcRc, -0S (0) Rd, -0S (0) 2Rd, -0S (0) 20Rd, -OS (0) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (N0H) Ra, -C (N0H) NRcRc, -0C (0) Rd, -0C (0) 0Rd, - 0C (0) NRcRc; 0C (NH) NRcRc, -0C (NRa) NRcRc, - [NHC (0)] nRd, - [NRaC (0)] pRd, - [NHC (0)] n0Rd, - [NRaC (0)] p0Rd, - [NHC (0)] pNRcRc, - [NRaC (O)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently a protecting group or Ra, alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more thereof or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently a protective group or Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; with the proviso that N 4 - (2,2-Dimethyl-3-oxo-4 H -5-pyrid [1,4] oxazin-6-yl) -N 2 - (3-chloro-4-methoxyphenyl) -5-fluoro- 2,4-pyrimidinediamine; N 4 - (2, 2-Dimethyl-3-oxo-4 H -5-pyrid [1,4] oxazin-6-yl) - N 2 - (3,5-dimethoxyphenyl) -5-fluoro-2,4-pyrimidinediamine; N2- (3,4-Dichlorophenyl) -N4- (2, 2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2,4-pyrimidinediamine; N4- (2,2-Dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -N2- (3-fluoro-4-methoxyphenyl) -5-fluoro-2, 4- pyrimidindiamine; N2- (3,5-Dichlorophenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2,4-pyrimidinediamine; N2- (3-Chloro-4-trifluoromethoxyphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2, 4- pyrimidindiamine; N2- (3-Chloro-4-methoxy-5-methylphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro- 2,4-pyrimidinediamine; N2- (3-Chloro-4-hydroxy-5-methylphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro- 2,4-pyrimidinediamine; and N2- (3,5-Dimethyl-4-methoxyphenyl) -N4- (2,2-dimethyl-3-oxo-4H-5-pyrid [1,4] oxazin-6-yl) -5-fluoro-2 , 4-pyrimidindiamine are not included.

10. A compound according to the structural formula: and salts, hydrates, solvates, N-oxides and prodrugs thereof, characterized in that R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, cycloalkyl (C3-C8) optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R groups and 5-15 elements heteroaryl, optionally substituted with one or more of the same od R5a is aryl (C5-C10) optionally substituted with one or more of the same or different R8 groups, or phenyl optionally substituted with one or more of the same or different R8 groups; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -ORa substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH2) m-Rb, - (CHRa) m-Rb, -0- (CH2) ffl-Rb, -S- (CH2) m -Rb, 0-CHRaRb, -0- CRa (Rb) 2, -O- (CHRa) m-Rb -0- (CH2) ffl-CH [(CH2) JJ1Rb] Rb, -S- (CHRa) m -Rb, -C (0) NH- ( CH2) m-Rb, -C (0) NH- (CHRa) J! I-Rb, -0- (CR2) mC (0)? M- (CEz) m-Kb, -S- (CH2) ffl- C HON-YCHsy ^ -R13, -0- (CHRa)? PC (0) NH- (CHRa) m-Rb, -S- (CHRa) jn-C (0) NH- (CHRa) ffl-Rb, -NH - (CH2) m-Rb, -NH- (CHRa) m-Rb, NH [(CH2) fflRb], -N [(CH2) mRb] 2, -NH-C (O) -NH- (CH2) m -Rb, -NH-C (O) - (CH2) ffl-CHRbRb and -NH- (CH2) aC (O) -NH- (CH2) ffl-Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-CIO), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2R, -0S (0) 20Rd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (N0H) NRcRc, -0C (0) Rd, -0C (0) 0Rd, - 0C (0) NRcRc; OC (NH) NRcRc, -OC (NRa) NRcRc, - [NHC (0)] pR, - [NRC (O)] nRd, - [NHC (O)] nORd, ~ [NRaC (0)] p0Rd, - [NHC (0)] pNRcRc, - [NRaC (0)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] nNRcRc; each Rc is independently Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different heteroatoms additional, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; every? is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; R35 is a suitable hydrogen or R8; and R45 is a (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups.

11. A compound according to the structural formula: and salts, hydrates, solvates and N-oxides thereof, characterized in that R is selected from the group consisting of wherein each R21 is independently a halogen atom or an alkyl optionally substituted with one or more of the same or different halo groups, R22 and R23 are each, independently of each other, a hydrogen, methyl or ethyl atom optionally substituted with one or more of the same or different groups; R4 is a (C3-C8) cycloalkyl optionally substituted with one or more of the same or different groups R8; and R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or R, -0Ra substituted with one or more of the same or different Ra or Rb, -B (ORa) 2 , -B (NRCRC) 2, - (CR2) m-Rb, - (CHRa) m-Rb, -0- (CH2) ffl-Rb, -S- CHz -R13, 0-CHRaRb, -0-CRa (Rb) 2, -0- (CHRa) m -Rb -O-ÍCHsí ^ -CHfíCHzJ ^ jR13, - S- (CHRa) mRb, -C (0) NH- (CH2) mRb, -C (0) NH- (CHRa) J! -R -0- (CH2) mC (0) NH- (CH2) ^ -R -S- (CH2) m C (0) NH- (CH2) J !! - Rb, -0- (CHRa) jp-C (0) NH- (CHRa) ffl-Rb, -S- (CHRa) ra-C (0) NH- (CHRa) J7! -Rb, -NH- (CH2) m-Rb, -NH- (CHRa) aRb, NH [(CH2) ffiRb], -N [(CH2) raRb] 2, -NH-C (0) -NH- (CH2) m-Rb, -NH-C (O) - (CH2) m-CHRbRb and -NH- (CH2) mC (0) -NH- (CH2) m-Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -OS (0) 2ORd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, - OC (0) NRcRc; OC (NH) NRcRc, -OC (NRa) NRcRc, - [NHC (0)] nRd, - [NRaC (O)] nRd, - [NHC (O)] OORd, - [NRaC (0)] OORd, - [NHC (0)] nNRcRc, - [NRaC (O)] pNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different heteroatoms additional, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

12. A compound according to the structural formula: and salts, hydrates, solvates and N-oxides thereof, characterized in that R2 is selected from the group consisting of alkyl (C1-C6) optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more thereof or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted by one or more of the same or different R8 groups, and heteroaryl of 5-15 elements optionally substituted with one or more of the same or different R8 groups; R4 is selected from the group consisting of hydrogen, (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different groups R8, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different groups R8, aryl (C5-C15) optionally substituted with one or more thereof or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl optionally substituted with one or more of the same or different R8 groups; and R8 is selected from the group consisting of R, Rb, Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or Rb, -B (ORa) 2 , -B (NRCRC) 2, - (CH2) m-Rb, - (CHRa) m-Rb, -0- (CH2) m-Rb, -S- CH ^ -R13, -0-CHRaRb, -0-CRa (Rb) 2, -O-ÍCHR3) *, - Rb -O-ÍCHZ ^ -CH? CH ^ R ^ R15, -S-ICHR ^ -R13, -C (O) NH- (CH2) m-Rb, -C (0) NH ~ (CHRa) ffl-Rb, -O-ÍCHz -CÍOJNH- CH ^ -R13, _s_ (CH2) jp-C (0) NH- (CH2) ffl-Rb, -O- (CHRa) ffl-C (O) NH- (CHRa) m-Rb, S- (CHRa) mC ( 0) NH- (CHRa)? P-Rb, -NH- (CH2) m-Rb, -NH- (CHRa) m-Rb, NH [(CH2) fflRb], -N [(CH2) raRb] 2, -NH-C (O) -NH- (CH2) ffl-Rb, -NH-C (O) - (CH ^ -CHR1 ^ and -NH- (CH2) aC (O) -NH- (CH2) m- Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-) C16), benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; is a suitable group selected independently of the group consisting of = 0, -ORd, haloal (C 1 -C 3) -alkyloxy, -0CF 3, = S, -SRd, = NRd, = N 0 Rd, -NRCRC, halogen, -CF 3, -CN, -NC, -OCN, -SCN, -NO, -N02, = N 2 , -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc, -S (0) 2NRcRc, -0S (0) Rd, -0S (0) ) 2Rd, -0S (0) 20Rd, -OS (0) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (N0H) NRcRc, -0C (0) Rd, -0C (0) 0Rd, -0C (0) NRcRc; 0C (NH) NRcRc, -0C (NRa) NRcRc, - [NHC (O)] pRd, - [NRaC (O)] pRd, - [NHC (O)] n0Rd, - [NRaC (0)] pORd, - [NHC (0)] nNRcRc, - [NRaC (O)] ONRCRC, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different heteroatoms additional, and which is optionally substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3; and R55 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8, cyclohexyl groups optionally substituted with one or more of the same or different groups R8, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different groups R8, aryl (C5-C15) optionally substituted with one or more thereof or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 elements heteroaryl optionally substituted with one or more of the same or different R8 groups.

13. A compound in accordance with the structural formula and salts, hydrates, solvates and N-oxides thereof, characterized in that R2 is R4 is selected from the group consisting of hydrogen, (C1-C6) alkyl optionally substituted with one or more of the same or different R groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different groups R8, cyclohexyl optionally substituted with one or more of the same or different groups R8, cycloheteroalkyl of 3-8 elements, optionally substituted with one or more of the same or different groups R8, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl optionally substituted with one or more of the same or different R8 groups; and R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -ORa substituted with one or more of the same or different Ra or Rb, -B (ORa) 2 , -B (NRCRC) 2, - (CH ^ -R13, - (CHRa) m-Rb, -0- (CH2) ffi-Rb, -S- (CH2) ra-Rb, -0-CHRaRb, -0-CRa (Rb) 2, -O- (CHRa) m -Rb -0- (CH2) ffl -CH [(CH2) i! Rb] Rb, -S- (CHRa) m-Rb, -C (O) NH- (CH2) m -Rb, -C (0) NH- (CHRa) m-Rb , -O-ÍCHsJ ^ -CÍONH-ÍCHzJ ^ -R15, -S- (CH2) ffl- CtOJNH-ÍCHz) ^, -0- (CHRa) ffl-C (0) NH- (CHRa) J7¡-Rb, -S- (CHRa) ffl-C (0) NH- (CHRa) ffl-Rb, -NH- (CH2) m -Rb, -NH- (CHRa) ffl-Rb, NH ^ CH ^ R13], -N [(CH2) fflRb] 2, -NH-C ^ -NH-ICH ^ -R15, -NH-C (O) - (CH2) ffl-CHRbRb and -NH- (CH2) mC (O) -NH- ( CR2) m-Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-CIO), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -OS (0) 2ORd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, - OC (0) NRcRc; OC (NH) NRcRc, -OC (NRa) NRcRc, - [NHC (0)] pRd, - [NRaC (O)] nRd, - [NHC (O)] pORd, ~ [NRaC (0)] n0Rd, - [NHC (0)]? NRCRC, - [NRaC (O)] pNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different heteroatoms additional, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3; and R35 is individually a hydrogen or R8.

14. A 2,4-pyrimidinediamine compound in accordance with the structure: and salts, hydrates, solvates and N-oxides thereof, characterized in that R2 is a phenyl group or indazole group, substituted with one or more of the same R8 groups; R5 is a fluorine atom; R6 is a hydrogen atom; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or R, -OR substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH2) m -Rb, - (CHRa) ffl-Rb, -O-ÍCHs ^ -R13, -S-ÍCH ^ -R, -0-CHRaRb, -0-CRa (Rb) 2, -0- (CHRa) 2¡J-Rb -0- (CR2) m-CR [(Cñ2) aRh] Rbr S- (CHRa) m-Rb, -C (0) NH- (CH2) m -Rb, -C (0) NH- (CHRa) ffl-Rb, -0- (CH2) i1-C (0) NH- (CH2) ¡I-Rb, -S- (CR2) m ~ C (0) NH- (CH2) ffl-Rb, -0- (CHRa) mC (0) NH- (CHRa)? NR, -S- (CHRa) jp-C (0) NH- (CHRa) ffl- Rb, -NH- (CH2) ffl-Rb, -NH- (CHRa) m-Rb, NH [(CH2) -DRb], -N [(CH2)] BRb] 2, -NH-C (O) - NH- (CH2) m-Rb, -NH-C (O) - (CH2) a, -CHRbRb and -NH-CHCHz ^ -CÍOÍ-NH-ÍCHsJ ^ -R13; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -ORd, haloalkyloxy (C1-C3), = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, -CN, - NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc, -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -OS (0) 2ORd, -OS (0) 2NRcRc, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, - C (NRa) NRCRC, -C (NOH) Ra, C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, -OC (0) NRcRc; OC (NH) NRcRc, OC (NRa) NRcRc, - [NHC (0)] pRd, - [NRaC (O)] ORd, - [NHC (O)] pORd, [NRaC (0)] pORd, - [NHC (0)] pNRcRc, - [NRaC (O)] ONRCRC, [NHC (NH)] nNRcRc and - [NRaC (NRa)] nNRcRc; each Rc is independently a protecting group or Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

15. The compound according to claim 14, characterized in that R2 is a di or tri-substituted phenyl group.

16. The compound according to claim 15, characterized in that one or more of the groups R8 are selected from the group consisting of halogens and alkoxy groups.

The compound according to claim 16, characterized in that the 2,4-pyrimidinediamine compound is 1256, 1257, 1258, 1259 or 1260.

18. A 2,4-pyrimidinediamine compound according to the structure: and salts, hydrates, solvates and N-oxides thereof, phenyl R5 is a fluorine atom; R6 is a hydrogen atom; R11 and R12 are each, independently from each other, selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, haloalkoxy, aminoalkyl and hydroxyalkyl; R35 is hydrogen or R8; and R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -ORa substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH ^ -R13, - (CHRa) m-Rb, -0- (CH2) ffl-Rb, -S- (CH2) m-Rb, -0-CHRaRb, -0-CRa (Rb) 2, -0- (CHRa) ffl- R -0- (CH2) m -CH [(CH2) J! Rb] Rb, -S- (CHRa) m-Rb, -C (O) NH- (CH2) m -Rb, -CYONH-ICHR ^ -R13, -0- (CH2 ) ffl-C (0) NH- (CH2) ja-Rb / -S- (CH2) ffl-C (0) NH- (CH2) mR, -0- (CHRa) mC (O) NH- (CHRa) m-Rb, -S- (CHRa) ffl-C (0) NH- (CHRa) m-Rb, -NH- (CH2) ffl-Rb, -NH- (CHRa) m-Rb, NH [(CH2) fflRb], -N [(CH2) fflRb] 2, -NH-C (0) -NH- (CH2) m -Rb, -NH-C (O) - (CH2) m-CHRbRb and -NH- (CH2 ) aC (0) -NH- (CH2) m-Rb; each R is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, ho-opiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, -CN, - NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc, -S (0) 2NRcRc, -0S (0) Rd, -OS (0) 2Rd, -0S (0) 20Rd, -0S (0) 2NRcRc, -C (0) Rd, -C (0) 0R, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (N0H) Ra, C (N0H) NRcRc, -0C (0) Rd, -0C (0) 0Rd, -0C (0) NRcRc; -OC (NH) NRCRC, -0C (NRa) NRcRc, - [NHC (0)], - [NRaC (0)] nRd, - [NHC (0)] n0Rd, - [NRaC (0)] p0Rd, - [NHC (0)] nNRcRc, - [NRaC (0)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] ONRCRC; each Rc is independently a protecting group or Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable R or Rb groups; each Rd is independently Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

19. The compound according to claim 18, characterized in that R35 is not a methyl group.

The compound according to claim 18, characterized in that the 2,4-pyrimidinediamine compound is 1000, 1001 or 1002.

21. A 2,4-pyrimidinediamine compound according to the structure: and salts, hydrates, solvates and N-oxides thereof, characterized in that R5 is a fluorine atom; R6 is a hydrogen atom; And it is selected from the group consisting of 0, S, SO, S02, SONR36, NH and NR37. Z is selected from the group consisting of O, S, SO, S02, SONR36, NH and NR37; each R35 is, independently of the others, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 are each, independently of each other, selected from the group consisting of hydrogen and R8; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or Rb, -B (0Ra) 2, -B (NRCRC) 2, - (CH2) ffl-Rb, - (CHRa) ffl-Rb, -O-ICHz ^ -R13, -S- CHz -R13, -0-CHRaRb, -0-CRa (Rb) 2, -0- (CHRa) ffl-Rb -0- (CH2) ¡! -CH [( CH2) fflRb] Rb, -S- (CHRa) ffl-Rb, -C (0) NH- (CH2) mR, -C (0) NH- (CHRa) ffl-R, -0- (CH2) ffl- C (0) NH- (CH2) JB-Rb -S-ÍCHz) ^ - C (0) NH- (CH2) ffl-Rb, -0- (CHRa) ffl-C (0) NH- (CHRa) ffi -Rb, -S- (CHRa) mC (0) NH- (CHRa) Jtl-Rb, -NH- (CH2) m -Rb, -NH- (CHRa) m-Rb, NH [(CH2) JBR], -N [(CH2) J] Rb] 2, -NH-C (0) -NH- (CH2) m -Rb, -NH-C (O) - (CH2) a -CHRR and -NH- (CH ^ -C (0) -NH- (CH2) m-Rb, each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11) , aryl (C5-CIO), phenyl, arylalkyl (C6-C16), benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, -CN, - NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc, -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -OS (0) 2ORd, -OS (0) 2NRcRc, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, C (NOH) NRcRc, -OC (0) Rd, -0C (0) 0Rd, -0C (0) NRcRc; OC (NH) NRcRc, OC (NRa) NRcRc, - [NHC (O)] pRd, - [NRaC (O)] nRd, - [NHC (O)] nORd, [NRaC (0)] nORd, - [NHC (0)] nNRcRc, - [NRaC (O)] pNRcRc, [NHC (NH)] nNRcRc and - [NRaC (NRa)]? NRCRC; each Rc is independently a protecting group or Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or R groups; each Rd is independently a Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3; R36 is hydrogen or alkyl; and R37 is selected from the group consisting of hydrogen and a progroup.

22. The compound according to claim 21, characterized in that Y is oxygen, Z is NH and one or more R35 is an alkyl group.

23. The compound in accordance with claim 21, characterized in that R is

24. The compound in accordance with claim 21, characterized in that R4 is

25. The compound according to claim 21, characterized in that Y is oxygen, Z is NH.

26. The compound according to claim 21, characterized in that the 2,4-pyrimidinediamine compound is 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231 , 232, 233, 234, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 1281, 1283, 1283, 1284, 1285, 1287, 1288, 1289, 1290 or 1291 .

27. A 2,4-pyrimidinediamine compound according to the structure: and salts, hydrates, solvates N-oxides thereof, characterized in that R2 is where Y is O, S, SO, S02, SONR36, NH, NR37; or NR35; R is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different groups R8, cyclohexyl optionally substituted with one or more of the same or different groups R8, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different groups R8, aryl (C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different R8 groups, and 5-15 element heteroaryl optionally substituted with one or more of the same or different R8 groups, R5 is a fluorine atom; R6 is a hydrogen atom; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or Rb, -B (0Ra) 2, -B (NRCRC) 2, - (CH2) ffl-R, - (CHRa) m-Rb f -0- (CR2) m-Rb, -S- (CH2) m-Rb, -0-CHRaRb, -0-CRa (Rb) 2, -0- (CHRa) a -Rb -0- (CR2) m -CR [(CR2) mRb] Rb, -S- (CHRa) mRb, -C (0) NH- (CH2) mRb, -C (0) NH- (CHRa) jp-Rb, -0 - (CH2) ffl-C (0) NH- (CH2) ffl-Rb, -S- (CH2) ffl- C (0) NH- (CH2) mR, -0- (CHRa) J7¡-C (0 ) NH- (CHRa) jp-Rb, -S- (CHRa) J7! -C (0) NH- (CHRa) m -Rb, -NH- (CH2) m -Rb, -NH- (CHRa) ra- Rb, NH [(CH2) fflRb], -N [(CH2) mRb] 2, -NH-C (0) -NH- (CH2) m -Rb, -NH-C (O) - (CH ^ -CHR1 ^ and -NH-ÍCHsJ ^ -CÍO-NH-ÍCHzJ ^ -R13; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11) ), aryl (C5-C10), phenyl, arylalkyl (C6-C16), benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements, each Rb is a suitable group independently selected from the group consisting of = 0 , -ORd, haloalkyloxy (C1-C3), = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, -CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc, -S (0) 2NRcRc, -0S (0) Rd, -0S ( 0) 2Rd, -0S (0) 20Rd, -0S (0) 2NRcRc, -C (0) Rd, -C (0) ORd,-C (0) NRcRc '-C (NH) NR ° RC, -C (NRa) NRCRC, -C (NOH) Ra, C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, -OC (0) NRcRc; OC (NH) NRcRc, OC (NRa) NRcRc, - [NHC (0)] pRd, - [NRaC (O)] pRd, - [NHC (O)] n0Rd, [NRaC (0)] pORd, - [NHC (0)] nNRcRc, - [NRaC (O)] ONR ° RC, [NHC (NH)] nNRcRc and - [NRaC (NRa)] nNRcRc; each Rc is independently a protecting group or Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently a Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3; R35 is a hydrogen or R8; R36 is hydrogen or alkyl; and R37 is selected from the group consisting of hydrogen and a progroup.

The compound according to claim 27, characterized in that the 2,4-pyrimidinediamine compound is 1070, 1071, 1073, 1074, 1075, 1076, 1078, 1080, 1085, 1091 or 1092.

29. A compound 2, 4 -pyrimidindiamine in accordance with the structure: and salts, hydrates, solvates and N-oxides thereof, characterized in that R2 is selected from the group consisting of (C1-C6) alkyl optionally substituted with one or more of the same or different R8 groups, (C3-C8) cycloalkyl optionally substituted with one or more of the same or different R8 groups, cyclohexyl optionally substituted with one or more of the same or different R8 groups, cycloheteroalkyl of 3-8 elements optionally substituted with one or more of the same or different R8 groups, aryl ( C5-C15) optionally substituted with one or more of the same or different R8 groups, phenyl optionally substituted with one or more of the same or different groups R8 and heteroaryl of 5-15 elements, optionally substituted with one or more thereof or different R8 groups, R5 is a fluorine atom; R6 is a hydrogen atom; and R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -ORa substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH2) ffl-Rb, - (CHRa) m-Rb, -O-CHCH-R15, -S-CHCHzJ-R13, -0-CHRaRb, -0-CRa (R) 2, -0- (CHRa) ffl-Rb -S- (CHRa) m-Rb, - C (O) NH- (CR2) m-Rbf-C (0) NH- (CHRa) jn-Rb, -O-YCHzJ ^ -CÍO H-ÍCHzJ ^ -R13, -S-ÍCHs -C (0) NH - (CH2) m-Rb, -0- (CHRa) mC (0) NH- (CHRa) JI! -Rb, -S- (CHRa) JI-C (0) NH- (CHRa) ffl-Rb, -NH- (CH2) ffl-Rb, -NH- (CHRa) m-Rb, -N [(CH2) J1IRb] 2, -NH-C (0) -NH- (CH2) iH-Rb, -NH- C (O) - (CH2) ffl-CHRbRb and -NH- (CH2) mC (O) -NH- (CH2) m-Rb; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -ORd, haloalkyloxy (C1-C3), -OCF3, = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -OS (0) 2Rd, -0S (0) 20Rd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, - OC (0) NRcRc; OC (NH) NRcRc, -OC (NRa) NRcRc, - [NHC (O)] nRd, - [NRC (O)] nRd, - [NHC (O)] pORd, - [NRaC (0)] pORd, - [NHC (0)] pNRcRc, - [NRaC (O)] pNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently a protecting group or Ra, or alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more of the same or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or R groups; each Rd is independently a Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3.

30. The compound in accordance with claim 29, characterized in that R2 is each R46, R47 and R48 independently are selected from the group consisting of a hydrogen, alkyl, alkoxy, hydroxyl, halogen, isoxazole, piperazino, N-alkylpiperazino, morpholino and CH3NHC (0) CH20-, with the condition that R46, R47 and R48 are not all hydrogen and when one of R46, R47 or R48 is isoxazole, piperazino, N-alkylpiperazino, morpholino or CH3NHC (0) CH20, then the remaining R46, R47 or R48 are hydrogen .

31. The compound according to claim 29, characterized in that R2 is selected from group consisting of and each R21, R22 and R23 are each independently of each other, an alkyl group.

32. The compound according to claim 31, characterized in that R22 and R23 or R21 and R22 or R21, R22 and R23 are each methyl groups.

33. A 2,4-pyrimidinediamine compound in accordance with the structure: and salts, hydrates, solvates and N-oxides thereof, characterized in that R4 is selected from the group consisting of R5 is a fluorine atom; R6 is a hydrogen atom; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, -0Ra substituted with one or more of the same or different Ra or Rb, -B (ORa) 2, -B (NRCRC) 2, - (CH2) ffl-R, - (CHRa) m-Rb, -0- (CH2) ffl-R, -S- (CH2) m-Rb, -0-CHRaRb, -0-CRa (R) 2, -0- (CHRa) ffl-Rb -S- (CHRa) m -Rb, -C (O) NH- (CH2) m -Rb, -C (0) NH- (CHRa) ffl-Rb, -0- (CH2) ffl-C (0) NH- (CH2) D! -Rb, -S-ÍCHz) ^ - CÍOjNH-ÍCHsí ^ -R15, -0- (CHRa)?! - C (0) NH- (CHRa) ffl-Rb, -S- (CHRa) J !! - C (0) NH- (CHRa) JI-Rb, -NH- (CH2) m-Rb, -NH- (CHRa) m-Rb, NH [(CH2) JBRb], -N [(CH2) mRb] 2 , -NH-C (O) -NH- (CH2) m-Rb, -NH-C (O) - (CH2) 1B-CHRbRb and - H- CHz ^ -CIOJ- H- CH ^ -R13; R21 is an alkyl group; R23 is an alkyl group; each R28 individually is a halogen or alkoxy; R29 is a (C1-C6) alkyl or (C3-C9) cycloalkyl; X is selected from the group consisting of N and CH; And it is selected from the group consisting of 0, S, SO, S02, SONR36, NH and NR37; Z is selected from the group consisting of 0, S, SO, S02, SONR36, NH and NR37; each R35 is, independently of the others, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 are each, independently of each other, selected from the group consisting of hydrogen and R8; each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl; each R37 is independently selected from the group consisting of hydrogen and a progroup; R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-C10), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = N0Rd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 20Rd, -S (0) NRcRc , -S (0) 2NRcRc, -0S (0) Rd, -0S (0) 2Rd, -0S (0) 20Rd, -OS (0) 2NRCRC, -C (0) Rd, -C (0) 0Rd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (N0H) Ra, -C (NOH) NRcRc, -OC (0) Rd, -0C (0) 0Rd, - 0C (0) NRcRc; 0C (NH) NRcRc, -OC (NRa) NRcRc, - [NHC (O)] pRd, - [NRaC (0)] nRd, - [NHC (0)] n0Rd, ~ [NRaC (0)] n0Rd, - [NHC (0)] nNRcRc, - [NRaC (0)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] ONRCRC; each Rc is independently a protecting group or Ra, alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more thereof or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable Ra or Rb groups; each Rd is independently a protective group or Ra; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

34. The compound according to claim 33, characterized in that R28 is a methoxy.

35. The compound according to claim 33, characterized in that R21 is a methyl group.

36. The compound according to claim 33, characterized in that each R28 is a chlorine.

37. The compound according to claim 33, characterized in that R21 is a methyl group and R28 is a chloro.

38. A 2,4-pyrimidinediamine compound according to the structure: and salts, hydrate, solvates and N-oxides thereof, characterized in that R4 is selected from the group consisting of R5 is a fluorine atom; R6 is a hydrogen atom; R8 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different groups Ra or Rb, -0Ra substituted with one or more of the same or different R 'Rb, -B (ORa) 2 , -B (NRCRC) 2, - (CHz ^ -R13, - (CHRa) m-Rb, -O-ICHz ^ ^ -R13, -S- (CH2) ffl-Rb, -0-CHRaRb, -0-CRa (R) 2, -0- (CHRa) J! -Rb -O-tCHzJa-CHt (CH2) fflRb] Rb, -S- (CHRa) m -Rb, -C (0) NH- (CH2) m -Rb, -C (0) NH- (CHRa) ffl-Rb, -O- (CH2) aC (O) NH- (CH2) m -Rb, -S- (CH2) ffl-C (O) NH- (CH2) m-Rb, -O- (CHRa) J !! -C (O) NH- (CHRa) m -Rb, -S- (CHRa)? R¡-C (0) NH- (CHRa) m -Rb, -NH- (CH2) ffl-Rb, -NH- (CHRa) ffl-Rb, -NH [(CH2) fflRb ], -NtÍCHzí ^ R ^ z, -NH-C (O) -NH- (CH2) m ~ Rb r -NH-C (O) - (CH2) ffl-CHRbRb and -NH- (CH2) mC (O ) -NH- (CH2) ffl-Rb; R21 is an alkyl group; each R28 individually is a halogen or alkoxy; X is selected from the group consisting of N and CH; And it is selected from the group consisting of O, S, SO, S02, SONR36, NH and NR37; Z is selected from the group consisting of O, S, SO, S02, SONR36, NH and NR37; each R35 is, independently of the others, selected from the group consisting of hydrogen and R8, or, alternatively, two R35s attached to the same carbon atom, are taken together to form an oxo (= 0), NH or NR38 group and the other two R35 are each, independently of each other, selected from the group consisting of hydrogen and R8; each R36 is independently selected from the group consisting of hydrogen and (C1-C6) alkyl; each R37 is independently selected from the group consisting of hydrogen and a progroup; R38 is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl; each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, cycloalkylalkyl (C4-C11), aryl (C5-CIO), phenyl, arylalkyl (C6-C16) , benzyl, heteroalkyl of 2-6 elements, cycloheteroalkyl of 3-8 elements, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, cycloheteroalkylalkyl of 4-11 elements, heteroaryl of 5-10 elements and heteroarylalkyl of 6-16 elements; each Rb is a suitable group independently selected from the group consisting of = 0, -0Rd, haloalkyloxy (C1-C3), -0CF3, = S, -SRd, = NRd, = NORd, -NRCRC, halogen, -CF3, - CN, -NC, -OCN, -SCN, -NO, -N02, = N2, -N3, -S (0) Rd, -S (0) 2Rd, -S (0) 2ORd, -S (0) NRcRc , -S (0) 2NRcRc, -OS (0) Rd, -0S (0) 2Rd, -0S (0) 20Rd, -OS (O) 2NRCRC, -C (0) Rd, -C (0) ORd, -C (0) NRcRc '-C (NH) NRCRC, -C (NRa) NRCRC, -C (NOH) Ra, -C (NOH) NRcRc, -OC (0) Rd, -OC (0) ORd, - OC (0) NRcRc; -OC (NH) NRCRC, -OC (NRa) NRcRc, - [NHC (0)] nRd, - [NRaC (O)] nRd, - [NHC (O)] OORd, - [NRaC (0)] pORd, - [NHC (0)] nNRcRc, - [NRaC (O)] nNRcRc, - [NHC (NH)] nNRcRc and - [NRaC (NRa)] pNRcRc; each Rc is independently a protecting group or Ra, alternatively, each Rc is taken together with the nitrogen atom to which it is attached, to form a cycloheteroalkyl or heteroaryl of 5-8 elements, which may optionally include one or more thereof or different additional heteroatoms, and which may optionally be substituted with one or more of the same or different suitable R or Rb groups; each Rd is independently a protective group or Ra; each m is independently an integer from 1 to 3; each n is independently an integer from 0 to 3; p is 1, 2 or 3; R50 is an alkyl group or - (CH2) qOH; q is an integer from 1 to 6; and R52 is an alkyl group or a substituted alkyl group.

39. The compound according to claim 38, characterized in that R21 is a methyl group.

40. The compound according to claim 38, characterized in that each R28 is a chlorine.

41. The compound according to claim 38, characterized in that R21 is a methyl group and R28 is a chloro.

42. The compound according to claim 38, characterized in that R50 is -CH2CH2OH.

43. The compound according to claim 38, characterized in that R52 is trifluoromethyl.

44. The compound according to claim 38, characterized in that R50 is a methyl group.

45. The compound according to claim 38, characterized in that each R28 is a chlorine.

46. The compound according to claim 38, characterized in that R50 is a methyl group and R28 is a chloro.

47. A 2,4-pyrimidinediamine compound according to the structure: and salts, hydrates, solvates and N-oxides thereof, characterized in that R 4 is cycloalkyl; R5 is a fluorine atom; R6 is a hydrogen atom; R21 is an alkyl group; and R30 is an alkyl group or a halogen.

48. The compound according to claim 47, characterized in that R21 is a methyl group.

49. The compound according to any of claims 1-48, characterized in that it further comprises a pharmaceutically acceptable carrier, diluent or excipient.

50. A method of treating or preventing an autoimmune disease and / or one or more symptoms associated therewith, characterized in that it comprises the step of administering to a subject suffering from an autoimmune disease or at risk of developing an autoimmune disease an effective amount of a 2,4-pyrimidinediamine compound according to any of claims 1-49.