WO2020185044A1 - 헤테로아릴 유도체 및 이를 유효성분으로 포함하는 약학적 조성물 - Google Patents
헤테로아릴 유도체 및 이를 유효성분으로 포함하는 약학적 조성물 Download PDFInfo
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- WO2020185044A1 WO2020185044A1 PCT/KR2020/003558 KR2020003558W WO2020185044A1 WO 2020185044 A1 WO2020185044 A1 WO 2020185044A1 KR 2020003558 W KR2020003558 W KR 2020003558W WO 2020185044 A1 WO2020185044 A1 WO 2020185044A1
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- amino
- pyrrolo
- pyrimidine
- methyl
- phenyl
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
- A23L29/045—Organic compounds containing nitrogen as heteroatom
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
Definitions
- Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of kinase-related diseases containing the compound, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
- X is CH or N
- R 1 is -H, halogen, cyano or haloalkyl
- R 2 is C 3-10 cycloalkyl, C 3-10 cycloalkenyl, -NHA 1 , or -OA 2
- a 1 is C 1-10 straight or branched chain alkyl, C 3-10 Of cycloalkyl, or a 3 to 9 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O, and S, wherein the alkyl, cycloalkyl and heterocycloalkyl are each independently halogen, C 1-5 straight or branched chain alkyl, C 3-10 cycloalkyl, C 1-4 straight or branched alkylsulfonyl, C 1-4 alkylaminosulfonyl and C 1-5 straight or branched Unsubstituted or substituted with one or more non-hydrogen substituents selected from the group consisting of chain alkoxy, wherein A 2 is C 3-10 cycloalkyl, wherein the cycloalkyl is C 1-3 straight or
- the R 3 is -H, C 1-6 straight or branched chain alkoxy or acrylamide, wherein the C 1-6 straight or branched chain alkoxy is unsubstituted or substituted with haloalkyl, and R 4 is -H or C 1-6 straight or branched chain alkoxy, or
- R 3 and R 4 form a 9 to 10 membered bicyclic ring containing one or more heteroatoms selected from the group consisting of N, O and S together with the benzene ring to which the carbon atom to which they are attached belongs,
- TTK TTK
- JAK2 JAK2
- SNARK YSK4, PRKCE
- CAMKK1 JNK3, TYK2, RSK2, CAMKK2
- YSK4 PRKCE
- ULK3, ULK1, RSK4, TRKB AAK1, GAK, SBK1, TYK2, CAMK2D, MAP3K2, KIT, FLT3, LRRK2, CSNK1D, CSNK1E, MEK4, RIOK1, DYRK1B, PKN2, SRPK2, JNK3, LRRK2, JNK3, LRRK2, JNK3 , JNK2, RIPK5, MEK3, ABL1, MAPKAPK2, GRK4 and SRPK3 provides a pharmaceutical composition for the prevention or treatment of one or more protein kinase-related diseases selected from the group consisting of.
- Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer containing the compound, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
- Another aspect of the present invention provides a method for treating cancer, comprising administering the compound, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof to an individual or subject in need thereof.
- the compound provided in one aspect of the present invention can significantly inhibit the proliferation of cancer cells by inhibiting a kinase, particularly TTK kinase, and thus for the prevention or treatment of cancer It can be usefully used as a pharmaceutical composition.
- embodiments of the present invention may be modified in various other forms, and the scope of the present invention is not limited to the embodiments described below.
- embodiments of the present invention are provided in order to more completely explain the present invention to those with average knowledge in the art.
- "including" a certain component throughout the specification means that other components may be further included, rather than excluding other components unless specifically stated to the contrary.
- halogen may be fluoro, chloro, bromo, or iodo.
- haloalkyl may mean a straight or branched chain alkyl (hydrocarbon) having a carbon atom substituted with one or more halogen atoms as defined herein.
- examples of the haloalkyl include, but are limited to, methyl, ethyl, propyl, isopropyl, isobutyl and N -butyl independently substituted with one or more halogen atoms, such as F, Cl, Br, I no.
- alkyl may mean a linear or branched acyclic saturated hydrocarbon consisting of carbon atoms.
- Representative -(C 1-8 alkyl) include -methyl, -ethyl, -N- propyl, -N- butyl, -N- pentyl and -N- hexyl, -N- heptyl and -N- octyl;
- Branched chain saturated alkyl is -isopropyl, -secondary (sec)-butyl, -isobutyl, -tert-butyl, -isopentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl , 2,3-dimethylbutyl, and the like.
- -(C 1-8 alkyl) may or may not be substituted.
- a C 1-8 alkyl group may be substituted with phenyl to form a benzyl group.
- cycloalkyl may refer to a non-aromatic saturated or unsaturated carbon ring.
- Representative cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, cycloheptyl, 1 ,3-cycloheptadienyl, 1,3,5-cycloheptatrienyl, cyclooctyl and cyclooctadienyl are included, but are not limited thereto.
- aryl may mean any functional group or substituent derived by removing one hydrogen from an aromatic hydrocarbon ring.
- the aryl group may be a monocyclic aryl group or a polycyclic aryl group.
- the number of ring carbon atoms in the aryl group may be 5 or more and 30 or less, 5 or more and 20 or less, or 5 or more and 15 or less.
- aryl group examples include phenyl group, naphthyl group, fluorenyl group, anthracenyl group, phenanthryl group, biphenyl group, terphenyl group, quarterphenyl group, quincphenyl group, sexyphenyl group, triphenylene group, pyrenyl group, benzofluoranthenyl group, and Although senilgi and the like can be illustrated, it is not limited to these.
- heteroaryl may be an aryl ring group including at least one of O, N, P, Si, and S as a heterogeneous element.
- the number of ring carbon atoms of the heteroaryl group may be 2 or more and 30 or less or 2 or more and 20 or less.
- Hetero aryl can be monocyclic hetero aryl or polycyclic hetero aryl.
- Polycyclic hetero aryl may have, for example, a bicyclic or tricyclic structure.
- heteroaryl examples include thienyl, thiophene, furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isothiazolyl, oxadiazolyl, triazolyl, pyridinyl, bipyridyl , Pyrimidyl, triazinyl, triazolyl, acridyl group, pyridazinyl group, pyrazinyl, quinolinyl, quinazoline, quinoxalinyl, phenoxazyl, phthalazinyl, pyrimidinyl, pyridopyrimidinyl , Pyrido pyrazinyl, pyrazino pyrazinyl, isoquinoline, indole, carbazole, imidazopyridazinyl, imidazopyridinyl, imidazopyrimidinyl, pyrazolopyrimidin
- the heteroaryl may also include an aryl ring fused to a heterocycloalkyl ring or a bicyclic heterocyclo-aryl including a heteroaryl fused to a cycloalkyl ring.
- One or more of the same or different substituents mentioned above may be substituted at the same position or different positions, and may be substituted sequentially.
- the meaning of “sequential” means that after one substituent is substituted in the formula, another substituent is continuously substituted on the substituent.
- a cycloalkyl group is substituted on the alkyl group, and the In the case where the carbonyl group is sequentially substituted in the cycloalkyl group, it may be indicated that the carbonyl group is sequentially substituted by naming it as carbonylcycloalkylalkyl.
- One aspect of the present invention provides a compound represented by the following Formula 1, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
- X is CH or N
- R 1 is -H, halogen, cyano or haloalkyl
- R 2 is C 3-10 cycloalkyl, C 3-10 cycloalkenyl, -NHA 1 , or -OA 2 ,
- a 1 is a 3 to 9 membered heterocyclo including one or more heteroatoms selected from the group consisting of C 1-10 straight or branched chain alkyl, C 3-10 cycloalkyl, or N, O, and S.
- Alkyl, the alkyl, cycloalkyl and heterocycloalkyl are each independently halogen, C 1-5 straight or branched chain alkyl, C 3-10 cycloalkyl, C 1-4 straight or branched alkylsulfonyl , Unsubstituted or substituted with one or more non-hydrogen substituents selected from the group consisting of C 1-4 alkylaminosulfonyl and C 1-5 linear or branched alkoxy,
- a 2 is C 3-10 cycloalkyl, wherein the cycloalkyl is unsubstituted or substituted with one or more non-hydrogen substituents of C 1-3 straight or branched chain alkyl and hydroxy,
- the R 3 is -H, C 1-6 straight or branched chain alkoxy or acrylamide, wherein the C 1-6 straight or branched chain alkoxy is unsubstituted or substituted with haloalkyl, and, R 4 Is -H or C 1-6 straight or branched chain alkoxy, or
- R 3 and R 4 form a 9 to 10 membered bicyclic ring containing one or more heteroatoms selected from the group consisting of N, O and S together with the benzene ring to which the carbon atom to which they are attached belongs,
- R 5 is -H, C 1-6 alkylaminocarbonyl, unsubstituted or substituted phenyl, oxooxazolidinonyl, dioxidothiazolidinyl, oxopyrrolidinyl, dioxidothiazinanyl, oxo Morpholinyl, or heteroaryl selected from the group consisting of pyrazolyl, triazolyl, thiazolyl, oxazolyl, pyridinyl and imidazolyl, wherein the heteroaryl is C 1-5 alkyl, halogen and Substituted or unsubstituted with one or more non-hydrogen substituents selected from the group consisting of 3 to 7 membered heterocycloalkyl including one or more hetero atoms selected from the group consisting of N, O, and S, or C 3-10 cyclo It may be fused with alkyl to form a bicyclic ring, and the substituted phenyl is substituted
- R 2 is C 3-8 cycloalkyl, C 3-6 cycloalkenyl, -NHA 1 , or -OA 2 , wherein, A 1 is a C 1-6 straight chain or Branched chain alkyl, C 3-7 cycloalkyl, or 3 to 6 membered heterocycloalkyl containing one or more O,
- a 1 is C 3-7 cycloalkyl
- the cycloalkyl is unsubstituted or substituted with one or more fluoro
- the R 3 and R 4 may form a 9 to 10 membered bicyclic ring including one or more O together with the benzene ring to which the carbon atom to which they are attached belongs, and more specifically, the 9 to 10 atom
- the bicyclic ring may be dihydrobenzodioxin or dihydrobenzofuran.
- R 5 is -H, C 1-3 alkylaminocarbonyl, unsubstituted or substituted phenyl, oxoxazolidinonyl, dioxidothiazolidinyl, oxopyrrolidinyl, dioxido Thiazinanyl, oxomorpholinyl, or pyrazolyl, triazolyl, thiazolyl, oxazolyl, pyridinyl and imidazolyl are heteroaryl selected from the group consisting of, wherein the heteroaryl is C 1-3 A bicyclic ring substituted or unsubstituted with one or more non-hydrogen substituents selected from the group consisting of 4 to 6 membered heterocycloalkyl including one or more of alkyl, fluoro, and O, or fused with C 3-5 cycloalkyl And the substituted phenyl is substituted with hydroxy or C 1-3 alkyl, wherein the C 1-3 alkyl is
- R 5 is -H
- R 1 is -H, chloro, fluoro, bromo, iodo, cyano or trifluoromethyl
- R 2 is C 3-7 cycloalkyl, cyclohexenyl, -NHA 1 , or -OA 2 ,
- a 1 is C 1-6 straight or branched chain alkyl, C 3-7 cycloalkyl, or 3 to 6 membered heterocycloalkyl including O,
- a 1 is C 1-6 straight or branched chain alkyl
- the alkyl is C 3-6 cycloalkyl, C 1-3 straight or branched alkylsulfonyl, C 1-3 alkylamino Unsubstituted or substituted with one or more non-hydrogen substituents selected from the group consisting of sulfonyl and C 1-3 linear or branched alkoxy,
- a 1 is C 3-7 cycloalkyl
- the cycloalkyl is unsubstituted or substituted with one or more fluoro
- a 1 is a 3 to 6 membered heterocycloalkyl including O
- the heterocycloalkyl is unsubstituted or substituted with one or more C 1-3 straight chain alkyl
- a 2 is C 3-6 cycloalkyl, wherein the cycloalkyl is unsubstituted or substituted with one or more non-hydrogen substituents of C 1-3 straight or branched chain alkyl and hydroxy groups,
- R 3 is -H, C 1-4 straight or branched chain alkoxy or acrylamide, wherein the C 1-4 straight chain alkoxy is unsubstituted or substituted with trifluoromethyl, and R 4 is- H or C 1-3 straight-chain alkoxy, or
- the R 3 and R 4 form a 9 to 10 membered bicyclic ring containing at least one O together with the benzene ring to which the carbon atom to which they are attached belongs,
- R 5 is -H, C 1-3 alkylaminocarbonyl, unsubstituted or substituted phenyl, oxoxazolidinonyl, dioxidothiazolidinyl, oxopyrrolidinyl, dioxidothiazinanyl, oxo Morpholinyl, or a heteroaryl selected from the group consisting of pyrazolyl, triazolyl, thiazolyl, oxazolyl, pyridinyl and imidazolyl, wherein the heteroaryl is C 1-3 alkyl, fluoro, And substituted or unsubstituted with one or more non-hydrogen substituents selected from the group consisting of 4 to 6 membered heterocycloalkyl containing at least one O, or fused with C 3-5 cycloalkyl to form a bicyclic ring,
- the substituted phenyl is substituted with hydroxy or C 1-3 alkyl, wherein the C 1-3 al
- R 6 may be -H, halogen or C 1-3 linear alkyl.
- R 2 is , , , ,
- R 5 is -H
- X is N
- R 3 is -H, C 1-4 linear or branched alkoxy or acrylamide, wherein the C 1-4 linear alkoxy is unsubstituted or substituted with trifluoromethyl,
- R 4 is -H or C 1-3 linear alkoxy
- Preparing a compound represented by Formula 1 by removing the SEM protecting group from the compound represented by Formula 4 prepared in the above step (STEP 5); It provides a method for preparing the compound represented by Formula 1, including.
- Hal is halogen
- SEM is a protecting group
- Step 1 is a step of preparing a compound represented by Formula AA by introducing R 1 from the compound represented by Formula 00.
- the reaction can be carried out in a DMF solvent, the reaction temperature can be carried out at about 0 to 25°C, and the reaction time can be carried out for about 30 minutes to 4 hours. Can be done.
- Step 3 is a step of preparing a compound represented by Formula 2 by introducing R 2 from the compound represented by Formula BB.
- the reaction can be carried out in an alcohol solvent, the reaction temperature can be carried out at about 80°C, and the reaction time can be carried out for about 12 to 24 hours. I can.
- Step 4 is a step of preparing a compound represented by Formula 4 by reacting a compound represented by Formula 2 with a compound represented by Formula 3.
- the reaction can be carried out in an alcohol solvent, the reaction temperature can be carried out at about 60 to 120°C, and the reaction time can be carried out for about 30 to 90 minutes, but if the reaction can proceed smoothly, the reaction can be carried out without limitation on the reaction conditions. Can be done.
- Step 5 is a step of preparing a compound represented by Formula 1 by removing the protecting group (-SEM) from the compound represented by Formula 4 prepared in Step 1. Since this step is a step of removing the protecting group (-SEM), it can be performed through a known method of removing the protecting group according to the type of protecting group. Examples of the protecting group include 2-(trimethylsilyl)ethoxymethyl group, trimethylsilyl group (TMS), benzyl group, or acetyl group.
- Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer containing a compound represented by Formula 1, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
- the compound may exhibit inhibitory activity against TTK kinase to prevent or improve cancer.
- the cancer may be applied without limitation if it is a known cancer, but some specific examples include pseudomyxoma, intrahepatic biliary tract cancer, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, cleft lip cancer, mycosis Sarcoma, acute myeloid leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian epithelial carcinoma, ovarian germ cell carcinoma, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colon cancer, chronic myelogenous leukemia, chronic lymphocytic leukemia, Retinoblastoma, choroidal melanoma, barter bulge cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, non-sinus cancer, non-small cell lung cancer, tongue cancer,
- the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be administered in various oral and parenteral formulations upon clinical administration.
- formulation it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc.
- lubricants such as magnesium stearate and talc are also used.
- composition containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient can be administered parenterally, and parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection It depends on how to do it.
- the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is mixed in water together with a stabilizer or buffer to prepare a solution or suspension, and the ampoule or vial unit dosage form It can be manufactured with
- the composition may be sterilized and/or contain adjuvants such as preservatives, stabilizers, hydrating agents or emulsification accelerators, salts and/or buffers for controlling osmotic pressure, and other therapeutically useful substances, which are conventional methods of mixing, granulation. It can be formulated according to the method of painting or coating.
- Formulations for oral administration include, for example, tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, and troches.
- These formulations include diluents (e.g., lactose , Dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (e.g. silica, talc, stearic acid and its magnesium or calcium salt and/or polyethylene glycol).
- Tablets may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases, boron such as starch, agar, alginic acid or sodium salt thereof. It may contain release or boiling mixtures and/or absorbents, colorants, flavoring agents, and sweetening agents.
- a binder such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases, boron such as starch, agar, alginic acid or sodium salt thereof. It may contain release or boiling mixtures and/or absorbents, colorants, flavoring agents, and sweetening agents.
- composition for preventing or treating cancer containing the compound represented by Formula 1, its optical isomer, or its pharmaceutically acceptable salt as an active ingredient is administered as an individual therapeutic agent or used in combination with other anticancer agents in use. I can.
- Another aspect of the present invention provides the compound, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof for use in the treatment of cancer.
- Another aspect of the present invention provides a use of the compound, a stereoisomer thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof for use in the manufacture of a drug for treating cancer.
- Step 4 2,4-Dichloro-7 - ((2- (ethoxy) methyl trimethylsilyl)) -7 H - pyrrolo [2,3-d] pyrimidine-5-carbonitrile (1.0 eq.) , DIPEA (2.9 equivalents) and methyl amine (1.5 equivalents) were dissolved in EtOH (0.25 M), and the reaction mixture was stirred at 80° C. for 16 hours. After completion of the reaction, the organic solvent was concentrated under reduced pressure and removed. The reaction product was dissolved in EtOAc, washed with 1 N HCl aqueous solution and brine, the remaining water was removed using Na 2 SO 4 and concentrated under reduced pressure to obtain the target compound as a yellow solid. (Yield: 90%)
Abstract
Description
실시예화합물 | TTK Activity | 실시예화합물 | TTK Activity | 실시예화합물 | TTK Activity | 실시예화합물 | TTK Activity |
1 | A | 50 | B | 97 | A | 138 | A |
2 | A | 51 | B | 98 | A | 139 | C |
3 | A | 53 | A | 99 | A | 140 | C |
7 | A | 54 | B | 100 | B | 141 | A |
8 | B | 55 | A | 101 | A | 142 | A |
9 | A | 56 | A | 102 | C | 143 | A |
10 | A | 57 | B | 103 | C | 144 | A |
11 | A | 58 | A | 104 | B | 145 | A |
12 | A | 59 | C | 105 | B | 146 | A |
13 | A | 60 | B | 106 | B | 147 | A |
14 | A | 61 | B | 107 | B | 148 | A |
15 | A | 63 | A | 108 | A | 149 | B |
16 | A | 64 | A | 109 | A | 150 | B |
17 | C | 65 | A | 110 | A | 151 | A |
18 | A | 66 | A | 111 | A | 152 | B |
19 | B | 67 | A | 112 | A | 153 | B |
20 | A | 68 | A | 113 | B | 154 | A |
21 | B | 69 | A | 114 | A | 155 | A |
22 | A | 70 | A | 115 | A | 156 | A |
23 | B | 71 | A | 116 | A | 157 | A |
24 | A | 72 | A | 117 | A | 158 | A |
25 | C | 73 | A | 118 | A | 159 | A |
26 | B | 75 | A | 119 | A | 162 | A |
27 | A | 76 | A | 120 | B | 163 | A |
28 | C | 79 | A | 121 | A | 164 | A |
29 | A | 82 | A | 122 | A | 165 | A |
30 | A | 83 | A | 123 | B | 166 | A |
31 | A | 84 | A | 124 | A | 167 | A |
32 | A | 85 | A | 125 | A | 168 | A |
33 | B | 86 | A | 126 | A | 169 | A |
35 | C | 87 | B | 127 | B | 170 | A |
38 | A | 88 | B | 128 | B | 171 | A |
39 | A | 89 | A | 129 | C | 172 | A |
40 | A | 90 | A | 130 | B | 173 | A |
41 | B | 91 | A | 131 | B | 174 | A |
42 | B | 92 | A | 132 | B | 175 | A |
43 | A | 93 | A | 133 | C | 176 | B |
44 | B | 94 | A | 134 | A | 177 | B |
46 | C | 95 | A | 136 | B | ||
49 | A | 96 | A | 137 | B |
실시예 화합물 | MDA-MB-231 Acitivity | 실시예 화합물 | MDA-MB-231 Acitivity | 실시예 화합물 | MDA-MB-231 Acitivity | 실시예 화합물 | MDA-MB-231 Acitivity |
1 | A | 46 | C | 92 | A | 134 | A |
2 | A | 49 | A | 93 | A | 136 | A |
3 | B | 50 | A | 94 | A | 137 | A |
4 | B | 51 | C | 95 | B | 138 | A |
5 | C | 53 | B | 96 | A | 139 | B |
6 | C | 54 | B | 97 | A | 140 | A |
7 | A | 55 | A | 98 | A | 141 | A |
9 | C | 56 | A | 99 | A | 142 | B |
10 | A | 57 | B | 100 | A | 143 | A |
11 | A | 58 | A | 101 | A | 144 | A |
12 | C | 59 | A | 102 | B | 145 | A |
14 | B | 60 | A | 103 | B | 146 | A |
16 | A | 61 | A | 104 | B | 147 | A |
17 | A | 63 | B | 105 | B | 148 | A |
18 | A | 64 | A | 106 | A | 149 | A |
19 | A | 65 | A | 107 | A | 150 | A |
20 | A | 66 | A | 108 | B | 151 | A |
21 | B | 67 | A | 109 | A | 152 | A |
22 | B | 68 | A | 110 | A | 153 | A |
23 | A | 69 | C | 111 | A | 154 | A |
24 | A | 70 | C | 112 | B | 155 | A |
25 | A | 71 | B | 113 | B | 156 | A |
26 | A | 72 | B | 114 | B | 157 | A |
27 | A | 73 | A | 115 | A | 158 | A |
28 | C | 74 | C | 116 | A | 159 | A |
29 | B | 75 | A | 117 | A | 160 | C |
30 | A | 76 | A | 118 | A | 161 | C |
31 | A | 77 | B | 119 | A | 162 | A |
32 | A | 78 | B | 120 | B | 163 | A |
33 | A | 79 | A | 121 | A | 164 | A |
34 | A | 80 | A | 122 | A | 165 | A |
35 | B | 81 | A | 123 | C | 166 | A |
36 | A | 82 | A | 124 | A | 167 | A |
37 | A | 83 | B | 125 | A | 168 | A |
38 | A | 84 | C | 126 | C | 169 | A |
39 | A | 85 | B | 127 | A | 170 | A |
40 | A | 86 | A | 128 | B | 171 | A |
41 | B | 87 | A | 129 | B | 172 | A |
42 | A | 88 | A | 130 | B | 173 | B |
43 | A | 89 | A | 131 | A | 174 | A |
44 | A | 90 | A | 132 | B | 175 | A |
45 | A | 91 | A | 133 | B | 176 | B |
177 | B |
실시예화합물 | HCT116 | BxPC3 | DU145 | A549 |
47 | A | A | A | A |
48 | A | A | A | A |
52 | B | B | B | B |
53 | B | B | B | B |
54 | B | B | B | B |
55 | A | A | A | A |
56 | A | A | A | A |
62 | B | B | B | B |
63 | A | A | A | A |
64 | A | A | A | A |
실시예화합물 | SHP-77 Activity | 실시예화합물 | SHP-77 Activity | 실시예화합물 | SHP-77 Activity | 실시예화합물 | SHP-77 Activity |
16 | A | 99 | A | 126 | C | 154 | A |
29 | B | 100 | A | 127 | A | 155 | A |
38 | A | 101 | A | 128 | A | 156 | A |
40 | A | 102 | B | 129 | B | 157 | A |
49 | A | 103 | B | 130 | B | 158 | A |
50 | A | 104 | B | 131 | A | 159 | A |
56 | A | 105 | B | 132 | B | 160 | C |
57 | A | 106 | A | 133 | B | 161 | C |
58 | A | 107 | A | 134 | A | 162 | A |
59 | A | 108 | B | 136 | A | 163 | A |
60 | A | 109 | A | 137 | A | 164 | A |
61 | A | 110 | A | 138 | A | 165 | A |
83 | B | 111 | A | 139 | A | 166 | A |
84 | C | 112 | A | 140 | A | 167 | A |
85 | A | 113 | B | 141 | A | 168 | A |
87 | A | 114 | B | 142 | B | 169 | A |
88 | A | 115 | A | 143 | A | 170 | A |
89 | A | 116 | A | 144 | A | 171 | A |
90 | A | 117 | A | 145 | A | 172 | A |
91 | A | 118 | A | 146 | A | 173 | A |
92 | A | 119 | A | 147 | A | 174 | A |
93 | A | 120 | B | 148 | A | 175 | A |
94 | A | 121 | A | 149 | A | 176 | B |
95 | A | 122 | A | 150 | A | 177 | B |
96 | A | 123 | B | 151 | A | ||
97 | A | 124 | A | 152 | A | ||
98 | A | 125 | B | 153 | A |
Kinase | 실시예 7 화합물 (% Cont @ 1uM) |
TTK | 0.25 |
JNK1 | 2 |
LRRK2(G2019S) | 2.7 |
JNK3 | 4.3 |
LRRK2 | 4.8 |
FLT3(D835V) | 5.6 |
JNK2 | 13 |
RIPK5 | 17 |
MEK3 | 18 |
ABL1(F317L)-nonphosphorylated | 28 |
MAPKAPK2 | 28 |
GRK4 | 29 |
SRPK3 | 30 |
Kinase | 실시예 64 화합물 (% Cont @ 1uM) | Kinase | 실시예 64 화합물(% Cont @ 1uM) |
JAK2(JH1domain-catalytic) | 0 | SBK1 | 5.7 |
SNARK | 0 | TYK2(JH2domain-pseudokinase) | 7.2 |
TTK | 0.25 | CAMK2D | 12 |
YSK4 | 0.3 | MAP3K2 | 13 |
JNK1 | 0.9 | KIT(V559D,V654A) | 14 |
FLT3(ITD,D835V) | 1.2 | LRRK2 | 14 |
PRKCE | 1.4 | FLT3(ITD) | 17 |
CAMKK1 | 1.6 | LRRK2(G2019S) | 17 |
JNK3 | 1.7 | CSNK1D | 19 |
TYK2(JH1domain-catalytic) | 1.7 | CSNK1E | 24 |
RSK2(Kin.Dom.1-N-terminal) | 1.9 | ABL1(F317L)-nonphosphorylated | 26 |
CAMKK2 | 2.2 | GRK4 | 26 |
ULK3 | 2.6 | MEK4 | 27 |
ULK1 | 3.1 | RIOK1 | 27 |
RSK4(Kin.Dom.1-N-terminal) | 3.7 | DYRK1B | 28 |
TRKB | 3.9 | MAPKAPK2 | 28 |
JNK2 | 4.1 | PKN2 | 28 |
AAK1 | 4.4 | SRPK3 | 28 |
GAK | 4.4 | RIPK5 | 30 |
효소 | Activity |
LRRK2 | <1000nM |
JNK1 | <100nM |
JNK2 | <100nM |
JNK3 | <100nM |
Claims (17)
- 하기 화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염:[화학식 1](상기 화학식 1에서,상기 X는 CH 또는 N이고;상기 R1은 -H, 할로젠, 사이아노 또는 할로알킬이며;상기 R2는 C3-10의 사이클로알킬, C3-10의 사이클로알켄일, -NHA1, 또는 -OA2이고,상기 A1은 C1-10의 직쇄 또는 분지쇄 알킬, C3-10의 사이클로알킬, 또는 N, O, 및 S로 이루어지는 군으로부터 선택되는 하나 이상의 헤테로원자를 포함하는 3 내지 9 원자의 헤테로사이클로알킬이며, 상기 알킬, 사이클로알킬 및 헤테로사이클로알킬은 각각 독립적으로 할로젠, C1-5의 직쇄 또는 분지쇄 알킬, C3-10의 사이클로알킬, C1-4의 직쇄 또는 분지쇄 알킬설폰일, C1-4의 알킬아미노설폰일 및 C1-5의 직쇄 또는 분지쇄 알콕시로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환되거나 비치환되고,상기 A2는 C3-10의 사이클로알킬이며, 여기서, 상기 사이클로알킬은 C1-3의 직쇄 또는 분지쇄 알킬 및 하이드록시 중 하나 이상의 비수소 치환기로 치환되거나 비치환되고,상기 R3은 -H, C1-6의 직쇄 또는 분지쇄 알콕시 또는 아크릴아마이드이고, 여기서, 상기 C1-6의 직쇄 또는 분지쇄 알콕시는 할로알킬로 치환되거나 비치환되고, 및 상기 R4는 -H 또는 C1-6의 직쇄 또는 분지쇄 알콕시이거나,R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 N, O 및 S로 이루어지는 군으로부터 선택되는 헤테로원자를 하나 이상 포함하는 9 내지 10 원자의 이환 고리(bicyclic ring)를 형성하며,상기 R5는 -H, C1-6의 알킬아미노카보닐, 비치환 또는 치환된 페닐, 옥소옥사졸리디논일, 다이옥시도싸이아졸리딘일, 옥소피롤리딘일, 다이옥시도싸이아지난일, 옥소모르폴린일, 또는 피라졸일, 트라이아졸일, 싸이아졸일, 옥사졸일, 피리딘일 및 이미다졸일로 이루어진 군으로부터 선택되는 헤테로아릴이고, 여기서, 상기 헤테로아릴은 C1-5의 알킬, 할로젠 및 N, O, 및 S로 이루어지는 군으로부터 선택되는 하나 이상의 헤테로 원자를 포함하는 3 내지 7 원자의 헤테로사이클로알킬로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환 또는 비치환되거나 C3-10의 사이클로알킬과 융합되어 이환 고리를 형성할 수 있고, 상기 치환된 페닐은 하이드록시로 치환되거나 C1-5의 알킬, N, O, 및 S로 이루어지는 군으로부터 선택되는 하나 이상의 헤테로 원자를 포함하는 3 내지 7 원자의 헤테로사이클로알킬, 및 C3-10의 사이클로알킬 또는 알킬카보닐이 순차적으로 치환된 것이며,상기 R6은 -H, 할로젠 또는 C1-10의 직쇄 또는 분지쇄 알킬이다.)
- 제 1항에 있어서,상기 R2는 C3-8의 사이클로알킬, C3-6의 사이클로알켄일, -NHA1, 또는 -OA2이고,상기 A1은 C1-6의 직쇄 또는 분지쇄 알킬, C3-7의 사이클로알킬, 또는 O를 하나 이상 포함하는 3 내지 6 원자의 헤테로사이클로알킬이며,여기서, 상기 A1이 C1-6의 직쇄 또는 분지쇄 알킬인 경우, 상기 알킬은 C3-6의 사이클로알킬, C1-3의 직쇄 또는 분지쇄 알킬설폰일, C1-3의 알킬아미노설폰일 및 C1-3의 직쇄 또는 분지쇄 알콕시로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환되거나 비치환되고,상기 A1이 C3-7의 사이클로알킬인 경우, 상기 사이클로알킬은 하나 이상의 플루오로로 치환되거나 비치환되며,상기 A1이 O를 포함하는 3 내지 6 원자의 헤테로사이클로알킬인 경우, 상기 헤테로사이클로알킬은 하나 이상의 C1-3의 직쇄 알킬로 치환되거나 비치환되고,상기 A2는 C3-6의 사이클로알킬이며, 여기서, 상기 사이클로알킬은 C1-3의 직쇄 또는 분지쇄 알킬 및 하이드록시기 중 하나 이상의 비수소 치환기로 치환되거나 비치환되는 것인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 1항에 있어서,상기 R3은 -H, C1-4의 직쇄 또는 분지쇄 알콕시 또는 아크릴아마이드이고, 여기서, 상기 C1-4의 직쇄 알콕시는 트라이플루오로메틸로 치환되거나 비치환되고, 및 상기 R4는 -H 또는 C1-3의 직쇄 알콕시이거나,상기 R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 O를 하나 이상 포함하는 9 내지 10원자의 이환 고리(bicyclic ring)를 형성하는 것인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 4항에 있어서,상기 R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 O를 하나 이상 포함하는 9 내지 10 원자의 이환 고리(bicyclic ring)를 형성하며, 상기 9 내지 10 원자의 이환 고리는 다이하이드로벤조다이옥신 또는 다이하이드로벤조퓨란인 것인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 1항에 있어서,상기 R5는 -H, C1-3의 알킬아미노카보닐, 비치환 또는 치환된 페닐, 옥소옥사졸리디논일, 다이옥시도싸이아졸리딘일, 옥소피롤리딘일, 다이옥시도싸이아지난일, 옥소모르폴린일, 또는 피라졸일, 트라이아졸일, 싸이아졸일, 옥사졸일, 피리딘일 및 이미다졸일로 이루어진 군으로부터 선택되는 헤테로아릴이고, 여기서, 상기 헤테로아릴은 C1-3의 알킬, 플루오로, 및 O를 하나 이상 포함하는 4 내지 6 원자의 헤테로사이클로알킬로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환 또는 비치환되거나 C3-5의 사이클로알킬과 융합되어 이환 고리를 형성할 수 있고, 상기 치환된 페닐은 하이드록시 또는 C1-3의 알킬로 치환되며, 여기서, 상기 C1-3의 알킬은 아세틸피페라진 또는 C3-6의 사이클로알킬피페라진이 치환된 것인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 1항에 있어서,상기 X가 CH인 경우,상기 R1은 사이아노 또는 트라이플루오로메틸이고;상기 R2는 -NHA1이고, 여기서 상기 A1은 C3-7의 사이클로알킬이며,상기 R3은 C1-6의 직쇄 또는 분지쇄 알콕시이고 상기 R4는 -H이거나, 상기 R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 O를 하나 이상 포함하는 9 내지 10원자의 이환 고리(bicyclic ring)를 형성하며,상기 R5는 옥소피롤리딘일이고, 및상기 R6은 -H인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 1항에 있어서,상기 X가 N인 경우,상기 R1은 -H, 클로로, 플루오로, 브로모, 아이오도, 사이아노 또는 트라이플루오로메틸이고,상기 R2는 C3-7의 사이클로알킬, 사이클로헥센일, -NHA1, 또는 -OA2이며,상기 A1은 C1-6의 직쇄 또는 분지쇄 알킬, C3-7의 사이클로알킬, 또는 O를 포함하는 3 내지 6 원자의 헤테로사이클로알킬이고,여기서, 상기 A1이 C1-6의 직쇄 또는 분지쇄 알킬인 경우, 상기 알킬은 C3-6의 사이클로알킬, C1-3의 직쇄 또는 분지쇄 알킬설폰일, C1-3의 알킬아미노설폰일 및 C1-3의 직쇄 또는 분지쇄 알콕시로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환되거나 비치환되고,상기 A1이 C3-7의 사이클로알킬인 경우, 상기 사이클로알킬은 하나 이상의 플루오로로 치환되거나 비치환되며,상기 A1이 O를 포함하는 3 내지 6 원자의 헤테로사이클로알킬인 경우, 상기 헤테로사이클로알킬은 하나 이상의 C1-3의 직쇄 알킬로 치환되거나 비치환되고,상기 A2는 C3-6의 사이클로알킬이며, 여기서, 상기 사이클로알킬은 C1-3의 직쇄 또는 분지쇄 알킬 및 하이드록시기 중 하나 이상의 비수소 치환기로 치환되거나 비치환되고,상기 R3은 -H, C1-4의 직쇄 또는 분지쇄 알콕시 또는 아크릴아마이드이고, 여기서, 상기 C1-4의 직쇄 알콕시는 트라이플루오로메틸로 비치환되거나 치환되고, 상기 R4는 -H 또는 C1-3의 직쇄 알콕시이거나,상기 R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 O를 하나 이상 포함하는 9 내지 10 원자의 이환 고리(bicyclic ring)를 형성하며,상기 R5는 -H, C1-3의 알킬아미노카보닐, 비치환 또는 치환된 페닐, 옥소옥사졸리디논일, 다이옥시도싸이아졸리딘일, 옥소피롤리딘일, 다이옥시도싸이아지난일, 옥소모르폴린일, 또는 피라졸일, 트라이아졸일, 싸이아졸일, 옥사졸일, 피리딘일 및 이미다졸일로 이루어진 군으로부터 선택되는 헤테로아릴이고, 여기서, 상기 헤테로아릴은 C1-3의 알킬, 플루오로, 및 O를 하나 이상 포함하는 4 내지 6 원자의 헤테로사이클로알킬로 이루어진 군으로부터 선택되는 하나 이상의 비수소 치환기로 치환 또는 비치환되거나 C3-5의 사이클로알킬과 융합되어 이환 고리를 형성할 수 있고, 상기 치환된 페닐은 하이드록시 또는 C1-3의 알킬로 치환되며, 여기서, 상기 C1-3의 알킬은 아세틸피페라진 또는 C3-6의 사이클로알킬피페라진이 치환된 것이며, 및상기 R6은 -H, 할로젠 또는 C1-3의 직쇄 알킬인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 1항에 있어서,상기 X가 N인 경우,상기 R1은 -H, 클로로, 사이아노 또는 트라이플루오로메틸이고,상기 R3은 -H, C1-4의 직쇄 또는 분지쇄 알콕시 또는 아크릴아마이드이고, 여기서, 상기 C1-4의 직쇄 알콕시는 트라이플루오로메틸로 비치환되거나 치환되고,상기 R4는 -H 또는 C1-3의 직쇄 알콕시이거나,상기 R3 및 R4는 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 O를 하나 이상 포함하는 9 내지 10 원자의 이환 고리(bicyclic ring)를 형성하고, 상기 9 내지 10 원자의 이환 고리(bicyclic ring)는 다이하이드로벤조다이옥신 또는 다이하이드로벤조퓨란이며,상기 R6은 -H, 할로젠 또는 C1-3의 직쇄 알킬인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 10항에 있어서,상기 X가 N이고, 상기 R3 및 R4가 이들이 결합된 탄소 원자가 속한 벤젠 고리와 함께 다이하이드로벤조다이옥신 또는 다이하이드로벤조퓨란의 이환고리를 형성하는 경우,상기 R1은 -H, 클로로, 사이아노 또는 트라이플루오로메틸이고,상기 R5는상기 R6은 -H인 것인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제 10항에 있어서,상기 X가 N이고, 상기 R3가 -H, C1-4의 직쇄 또는 분지쇄 알콕시 또는 아크릴아마이드이고, 여기서, 상기 C1-4의 직쇄 알콕시는 트라이플루오로메틸로 비치환되거나 치환되고, 및 상기 R4는 -H 또는 C1-3의 직쇄 알콕시인 경우,상기 R1은 -H, 클로로, 사이아노 또는 트라이플루오로메틸이며,상기 R2는상기 R6은 -H, 할로젠 또는 C1-3의 직쇄 알킬인,화학식 1의 화합물, 이의 이성질체, 이의 용매화물, 이의 수화물 또는 이의 약학적으로 허용가능한 염.
- 제1항에 있어서,상기 화학식 1로 표시되는 화합물은 하기 화합물 군으로부터 선택되는 어느 하나인, 화합물, 이의 입체 이성질체, 이의 수화물, 또는 이의 약학적으로 허용 가능한 염:(1)(S)-4-(sec-뷰틸아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (2)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (3)4-(사이클로헥실아미노)-2-((2-메톡시-4-(2-옥소옥사졸리디논-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (4)N 4-사이클로헥실-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (5)5-클로로-N 4-사이클로헥실-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (6)N 4-사이클로헥실-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (7)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (8)4-((사이클로펜틸메틸)아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (9)2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-(메틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (10)(R)-4-(Sec-뷰틸아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (11)4-(뷰틸아미노)-2-((2-에톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (12)2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-(네오펜틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (13)2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-((2-메톡시에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (14)2-((2-에톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-4-((2-(메틸설폰일)에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (15)2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)- 7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (16)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (17)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(싸이아졸-2-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (18)4-(사이클로헥실아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (19)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-(테트라하이드로-2H-피란-4-일)-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (20)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-(옥세탄-3-일)-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (21)2-((4'-((4-아세틸피페라진-1-일)메틸)-[1,1'-바이페닐]-4-일)아미노)-4-(사이클로헥실아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (22)4-(사이클로헥실아미노)-2-((4'-((4-사이클로프로필피페라진-1-일)메틸)-[1,1'-바이페닐]-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (23)2-((4'-((4-아세틸피페라진-1-일)메틸)-3-메톡시-[1,1'-바이페닐]-4-일)아미노)-4-(사이클로헥실아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (24)4-(사이클로헥실아미노)-2-((4-(6-플루오로피리딘-3-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (25)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-메틸-1H-1,2,3-트라이아졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (26)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-메틸-1H-1,2,4-트라이아졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (27)4-(사이클로헥실아미노)-2-((2-메톡시-4-(1-메틸-1H-1,2,4-트라이아졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (28)4-(사이클로펜틸아미노)-2-((2-아이소부톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (29)2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)-3-플루오로페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (30)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(1-메틸-1H-이미다졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (31)4-(사이클로헥실아미노)-2-((4-(6,7-다이하이드로-5H-피롤로[2,1-c][1,2,4]트라이아졸-3-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (32)4-(((1S,4S)-4-하이드록시-4-메틸사이클로헥실)옥시)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (33)4-(사이클로펜틸아미노)-2-((4-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조퓨란-7-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (34)4-(사이클로헥실아미노)-2-((4-(2,4-다이메틸-1H-이미다졸-1-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (35)4-(사이클로펜틸아미노)-2-((2-메톡시-5-메틸-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (36)4-(사이클로헥실아미노)-2-((2-에톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (37)4-(사이클로헥실아미노)-2-((4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (38)4-(사이클로펜틸아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (39)4-(사이클로헥실아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (40)2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (41)2-((4'-((4-아세틸피페라진-1-일)메틸)-3-메톡시-[1,1'-바이페닐]-4-일)아미노)-4-(사이클로펜틸아미노)- 7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (42)4-(사이클로펜틸아미노)-2-((4-(6-플루오로피리딘-3-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (43)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (44)4-(사이클로펜틸아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (45)4-(사이클로헥실옥시)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (46)4-사이클로프로필-2-((2-에톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (47)1-(4-((4-(사이클로펜틸아미노)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)피롤리딘-2-온; (48)1-(4-((4-(사이클로헥실아미노)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)피롤리딘-2-온; (49)4-((2-메톡시에틸)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (50)4-((사이클로펜틸메틸)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (51)1-(3-메톡시-4-((4-(메틸아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)페닐)피롤리딘-2-온; (52)1-(4-((4-(사이클로펜틸아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)피롤리딘-2-온; (53)1-(4-((4-(사이클로헥실아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)피롤리딘-2-온; (54)2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-4-(메틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (55)4-(사이클로펜틸아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (56)4-(사이클로헥실아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (57)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)-3-플루오로페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (58)2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)-3-플루오로페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (59)4-(사이클로헵틸아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (60)2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-(네오펜틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (61)4-(((1R,4S)-바이사이클로[2.2.1]헵탄-2-일)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (62)1-(4-((4-(사이클로헥실아미노)-3-(트라이플루오로메틸)-1H-피롤로[2,3-b]피리딘-6-일)아미노)-3-메톡시페닐)피롤리딘-2-온; (63)4-(사이클로펜틸아미노)-6-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-1H-피롤로[2,3-b]피리딘-3-카보나이트릴; (64)4-(사이클로헥실아미노)-6-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-1H-피롤로[2,3-b]피리딘-3-카보나이트릴; (65)4-(아이소프로필아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (66)4-(아이소뷰틸아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (67)4-(뷰틸아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (68)(S)-4-(sec-뷰틸아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (69)4-(사이클로뷰틸아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (70)4-((사이클로뷰틸메틸)아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (71)4-((사이클로펜틸메틸)아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (72)4-((1-메톡시-2-메틸프로판-2-일)아미노)-2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (73)2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-4-(옥세탄-3-일아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (74)2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (75)2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-(메틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (76)4-(아이소프로필아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (77)2-((2-메톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-4-(네오펜틸아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (78)4-(사이클로헥실아미노)-2-((2-에톡시-4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (79)4-(사이클로헥실아미노)-2-((8-(2-옥소피롤리딘-1-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (80)4-(사이클로헥실아미노)-2-((4-(2-옥소피롤리딘-1-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (81)4-(사이클로헥실아미노)-2-((2-메톡시-4-(3-옥소모르폴리노)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (82)4-(사이클로뷰틸아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (83)4-((2-(아이소프로필설폰일)에틸)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (84)2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-((2-(메틸설폰일)에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (85)2-((5-사이아노-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-4-일)아미노)-N,N-다이메틸에테인-1-설폰아마이드; (86)4-((5-클로로-4-(((1S,4S)-4-하이드록시-4-메틸사이클로헥실)옥시)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-N,N-다이메틸-3-(((R)-1,1,1-트라이플루오로프로판-2-일)옥시)벤즈아마이드; (87)4-(사이클로펜틸아미노)-6-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-1H-피롤로[2,3-b]피리딘-3-카보나이트릴; (88)4-(사이클로펜틸아미노)-6-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-1H-피롤로[2,3-b]피리딘-3-카보나이트릴; (89)2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (90)2-((2-메톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (91)2-((4-(3,5-다이메틸이소옥사졸-4-일)-2-메톡시페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (92)2-((2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (93)2-((2-메톡시-4-(2-메틸-1H-이미다졸-1-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (94)4-((2-메톡시에틸)아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (95)2-((2-메톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-4-((2-메톡시에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (96)2-((4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)아미노)-4-((2-메톡시에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (97)2-((2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-4-((2-메톡시에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (98)2-((2-메톡시-4-(2-메틸-1H-이미다졸-1-일)페닐)아미노)-4-((2-메톡시에틸)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (99)4-(사이클로프로필아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (100)4-((사이클로뷰틸메틸)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (101)(R)-4-((1-메톡시프로판-2-일)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (102)2-((4-(3,5-다이메틸아이소옥사졸-4-일)-5-플루오로-2-메톡시페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (103)4-(사이클로펜틸아미노)-2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (104)4-(사이클로펜틸아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-5-플루오로-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (105)4-(사이클로헥실아미노)-2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (106)N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-N 4-(테트라하이드로-2H-피란-4-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (107)N 2-(8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)-N 4-(테트라하이드로-2H-피란-4-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (108)1-(8-((4-((테트라하이드로-2H-피란-4-일)아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)피롤리딘-2-온; (109)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (110)4-((3,3-다이플루오로사이클로펜틸)아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (111)4-사이클로프로필-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (112)4-사이클로프로필-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (113)N 4-사이클로펜틸-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (114)N 4-사이클로펜틸-N 2-(8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (115)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (116)4-((3,3-다이플루오로사이클로펜틸)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (117)N 2-(2-메톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)-N 4-(테트라하이드로-2H-피란-4-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (118)N 2-(2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)-N 4-(테트라하이드로-2H-피란-4-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (119)2-((3-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (120)4-(사이클로펜틸아미노)-2-((3-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (121)4-(사이클로헥실아미노)-2-((3-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (122)2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (123)4-(사이클로헥실아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-5-플루오로-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (124)2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (125)4-(사이클로펜틸아미노)-2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (126)4-(사이클로헥실아미노)-2-((5-플루오로-2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (127)5-클로로-N 4-사이클로펜틸-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (128)5-클로로-N 4-사이클로펜틸-N 2-(8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (129)4-(사이클로헥세-1-엔-1-일)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (130)4-(사이클로헥세-1-엔-1-일)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (131)N 2-(4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)-N 4-(테트라하이드로-2H-피란-4-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (132)N 4-사이클로펜틸-N 2-(2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (133)N 4-사이클로펜틸-N 2-(8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (134)2-((3-메톡시-[1,1'-바이페닐]-4-일)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (135)2-((3-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (136)4-(사이클로펜틸아미노)-2-((3-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (137)4-(사이클로헥실아미노)-2-((3-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (138)2-((4-(3,5-다이메틸아이소옥사졸-4-일)-3-메톡시페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (139)4-(사이클로펜틸아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-3-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (140)4-(사이클로헥실아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-3-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (141)2-((3'-하이드록시-3-메톡시-[1,1'-바이페닐]-4-일)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (142)N-(2-((5-사이아노-4-(사이클로펜틸아미노)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-5-(1-메틸-1H-피라졸-5-일)페닐)아크릴아마이드; (143)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((2-메톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (144)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-4-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (145)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (146)4-(((1R,4S)-바이사이클로[2.2.1]헵탄-2-일)아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (147)4-(((1R,4S)-바이사이클로[2.2.1]헵탄-2-일)아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (148)4-(((1R,4S)-바이사이클로[2.2.1]헵탄-2-일)아미노)-2-((8-(2-옥소피롤리딘-1-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (149)4-(사이클로헵틸아미노)-2-((4-(3,5-다이메틸아이소옥사졸-4-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (150)4-(사이클로헵틸아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (151)4-(사이클로헵틸아미노)-2-((8-(2-옥소피롤리딘-1-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (152)4-((3,3-다이플루오로사이클로헥실)아미노)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (153)4-((3,3-다이플루오로사이클로헥실)아미노)-2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (154)4-((3,3-다이플루오로사이클로헥실)아미노)-2-((2-메톡시-4-(4-메틸-4H-1,2,4-트라이아졸-3-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (155)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (156)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (157)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)-2-메톡시페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (158)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (159)4-((3,3-다이플루오로사이클로펜틸)아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (160)2-((8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-(옥세탄-3-일아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (161)2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-(옥세탄-3-일아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (162)4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-2-((3-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (163)2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)-2-메톡시페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (164)2-((4-(1,1-다이옥시도-1,2-싸이아지난-2-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (165)2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)-2-메톡시페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (166)2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)페닐)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (167)(R)-2-((2-메톡시-4-(2-메틸-1H-이미다졸-1-일)페닐)아미노)-4-((1-메톡시프로판-2-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (168)(R)-2-((2-메톡시-4-(1-메틸-1H-피라졸-5-일)페닐)아미노)-4-((1-메톡시프로판-2-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (169)(R)-4-((1-메톡시프로판-2-일)아미노)-2-((8-(1-메틸-1H-피라졸-4-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (170)2-((2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-((테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (171)2-((2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)아미노)-4-((2,2-다이메틸테트라하이드로-2H-피란-4-일)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (172)N 4-(2,2-다이메틸테트라하이드로-2H-피란-4-일)-N 2-(8-(1-메틸-1H-피라졸-5-일)-2,3-다이하이드로벤조[b][1,4]다이옥신-5-일)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2,4-다이아민; (173)4-(사이클로펜틸아미노)-2-((4-(1,1-다이옥시도아이소싸이아졸리딘-2-일)-3-플루오로페닐)아미노)-7H-피롤로[2,3-d]피리미딘-5-카보나이트릴; (174)2-(3-메톡시-4-((4-((테트라하이드로-2H-피란-4-일)아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)페닐)아이소싸이아졸리딘 1,1-다이옥사이드; (175)2-(3-메톡시-4-((4-((테트라하이드로-2H-피란-4-일)아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)페닐)-1,2-싸이아지난 1,1-다이옥사이드; (176)2-(4-((4-(사이클로펜틸아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)아이소싸이아졸리딘 1,1-다이옥사이드; (177)2-(4-((4-(사이클로펜틸아미노)-5-(트라이플루오로메틸)-7H-피롤로[2,3-d]피리미딘-2-일)아미노)-3-메톡시페닐)-1,2-싸이아지난 1,1-다이옥사이드.
- 제 1항의 화학식 1로 표시되는 화합물, 이의 입체 이성질체, 이의 수화물, 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 암의 예방 또는 치료용 약학적 조성물.
- 제 14항에 있어서,상기 화합물은 JAK2, SNARK, TTK, YSK4, JNK1, FLT3, PRKCE, CAMKK1, JNK3, TYK2, RSK2, CAMKK2, ULK3, ULK1, RSK4, TRKB, LRRK2, JNK3, AAK1, GAK, SBK1, TYK2, CAMK2D, MAP3K2, KIT, CSNK1D, CSNK1E, MEK4, RIOK1, DYRK1B, PKN2, FLT3, JNK2, RIPK5, MEK3, ABL1, MAPKAPK2, GRK4 및 SRPK3로 이루어지는 군으로부터 선택되는 하나 이상의 단백질 키나아제에 대하여 저해 활성을 나타내는 것을 특징으로 하는 것인, 약학적 조성물.
- 제 14항에 있어서,상기 화합물은 TTK 키나아제에 대해 저해 활성을 나타내는 것을 특징으로 하는 것인, 약학적 조성물.
- 제 14항에 있어서,상기 암은 가성점액종, 간내 담도암, 간모세포종, 간암, 갑상선암, 결장암, 고환암, 골수이형성증후군, 교모세포종, 구강암, 구순암, 균상식육종, 급성골수성백혈병, 급성림프구성백혈병, 기저세포암, 난소상피암, 난소생식세포암, 남성유방암, 뇌암, 뇌하수체선종, 다발성골수종, 담낭암, 담도암, 대장암, 만성골수성백혈병, 만성림프구백혈병, 망막모세포종, 맥락막흑색종, 바터팽대부암, 방광암, 복막암, 부갑상선암, 부신암, 비부비동암, 비소세포폐암, 설암, 성상세포종, 소세포폐암, 소아뇌암, 소아림프종, 소아백혈병, 소장암, 수막종, 식도암, 신경교종, 신우암, 신장암, 심장암, 십이지장암, 악성 연부조직 암, 악성골암, 악성림프종, 악성중피종, 악성흑색종, 안암, 외음부암, 요관암, 요도암, 원발부위불명암, 위림프종, 위암, 위유암종, 위장관간질암, 윌름스암, 유방암, 삼중음성유방암, 육종, 음경암, 인두암, 임신융모질환, 자궁경부암, 자궁내막암, 자궁육종, 전립선암, 전이성 골암, 전이성뇌암, 종격동암, 직장암, 직장유암종, 질암, 척수암, 청신경초종, 췌장암, 침샘암, 카포시 육종, 파제트병, 편도암, 편평상피세포암, 폐선암, 폐암, 폐편평상피세포암, 피부암, 항문암, 횡문근육종, 후두암, 흉막암, 혈액암 및 흉선암으로 이루어진 군으로부터 선택되는 1종 이상인 것인, 약학적 조성물.
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AU2020236300A AU2020236300A1 (en) | 2019-03-13 | 2020-03-13 | Heteroaryl derivatives and pharmaceutical composition comprising same as active ingredient |
EA202192087A EA202192087A1 (ru) | 2019-03-27 | 2020-03-13 | Гетероарильные производные и содержащая их фармацевтическая композиция |
MX2021010970A MX2021010970A (es) | 2019-03-13 | 2020-03-13 | Derivados de heteroarilo, y composicion farmaceutica que los comprende. |
CN202080020325.XA CN113574057A (zh) | 2019-03-13 | 2020-03-13 | 杂芳基衍生物及包含其作为活性成分的药物组合物 |
US17/438,341 US20230183243A1 (en) | 2019-03-13 | 2020-03-13 | Heteroaryl derivatives and pharmaceutical composition comprising same as active ingredient |
JP2021548167A JP2022523351A (ja) | 2019-03-13 | 2020-03-13 | ヘテロアリール誘導体およびこれを有効成分として含む薬学的組成物 |
CA3130478A CA3130478A1 (en) | 2019-03-13 | 2020-03-13 | Heteroaryl derivatives, and pharmaceutical composition comprising the same as active ingredient |
BR112021017829A BR112021017829A2 (pt) | 2019-03-13 | 2020-03-13 | Composto, e, composição farmacêutica para uso em prevenir ou tratar câncer |
EP20768933.2A EP3915986A4 (en) | 2019-03-13 | 2020-03-13 | HETEROARYL DERIVATIVES AND PHARMACEUTICAL COMPOSITION COMPRISING THEM AS ACTIVE PRINCIPLE |
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BR112021017829A2 (pt) | 2021-11-30 |
EP3915986A1 (en) | 2021-12-01 |
EP3915986A4 (en) | 2023-01-25 |
CN113574057A (zh) | 2021-10-29 |
KR20200110250A (ko) | 2020-09-23 |
CA3130478A1 (en) | 2020-09-17 |
US20230183243A1 (en) | 2023-06-15 |
JP2022523351A (ja) | 2022-04-22 |
AU2020236300A1 (en) | 2021-09-16 |
MX2021010970A (es) | 2021-10-13 |
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