MXPA06008597A

MXPA06008597A - 2-(3-substituted-aryl)amino-4-aryl-thiazoles as tyrosine kinase inhibitors

Info

Publication number: MXPA06008597A
Application number: MXPA/A/2006/008597A
Authority: MX
Inventors: Marco Ciufolini; Camille Wermuth; Bruno Giethlen; Alain Moussy
Original assignee: Ab Science; Marco Ciufolini; Gielthen Bruno; Alain Moussy; Camille Wermuth
Priority date: 2004-01-30
Filing date: 2006-07-28
Publication date: 2007-04-10

Abstract

The present invention relates to novel compounds selected from 2-(3-substitutedaryl)amino-4-aryl-thiazoles that selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective c-kit inhibitors.

Description

2- (3-SUSTAINED-ARIL) AMINO-4-ARIL-TIAZOLES AS INHIBITORS OF TYROSINE KINASE DESCRIPTIVE MEMORY The present invention describes novel compounds selected from 2- (3-substituted-aryl) amino-4-aryl-thiazoles that selectively modulate, regulate and / or inhibit signal transduction mediated by certain native tyrosine kinases and / or mutants involved in a variety of human and animal diseases such as cellular proliferative, metabolic, allergic and degenerative disorders. More particularly, these compounds are potent and selective c-kit inhibitors. Tyrosine kinases are proteins of the receptor or non-receptor type, which transfer the terminal phosphate of ATP to protein tyrosine residues, thereby activating or inactivating the signal transduction pathways. These proteins are known to be involved in many cellular mechanisms, which in the case of rupture, lead to disorders such as abnormal cell proliferation and migration as well as inflammation. To date, there are about 58 known receptor tyrosine kinases. Other tyrosine kinases are the well-known VEGF receptors (Kim et al., Nature 362, pp 841-844, 1993), PDGF receptors, c-kit and the FLK family. These receptors can transmit signals to other tyrosine kinases including Src, Raf, Frk, Btk, Csk, Abl, Fes / Fps, Fak, Jak, Ack. etc. Among the tyrosine kinase receptors, kit-c is of special interest. Indeed, the c-kit is a main receptor that activates the mast cells, which have proven to be directly or indirectly involved in numerous pathologies for which the applicant has presented WO 03/004007, WO 03/004006, WO 03/003006, WO 03/003004, WO 03/002114, WO 03/002109, WO 03/002108, WO 03/002107, WO 03/002106, WO 03/002105, WO 03/039550, WO 03/035050, WO 03/035049, US 60 / 359,652 and US 60/359651. It has been found that mast cells present in patient tissues are involved in, or contribute to, the genesis of diseases such as autoimmune diseases (rheumatoid arthritis, inflammatory bowel diseases (IBD)), allergic diseases, tumor angiogenesis, inflammatory diseases, and cystitis. interstitial In these diseases, mast cells have been shown to participate in tissue destruction by releasing a cocktail of different proteases and mediators such as histamine, neutral proteases, lipid-derived mediators (prostaglandins, thromboxanes and leukotrienes), and several cytokines ( IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, TNF-a, GM-CSF, MIP-1a, MIP-1 b, MIP-2 and IFN -?) The c-kit receptor can also be constitutively activated by mutations that lead to abnormal cell proliferation and the development of diseases such as mastocytosis and various cancers.

For this reason, the objective c-kit has been proposed to decrease the mast cells responsible for these disorders. The main objective that remains implicit in the present invention is therefore to find potent and selective compounds capable of inhibiting wild type and / or mutated c-kit. Many different compounds have been described as tyrosine kinase inhibitors, for example, monocyclic, bicyclic or heterocyclic aryl bis compounds (WO 92/20642), vinylene-azaindole derivatives (WO 94/14808) and l-cyclopropii-4-pyridyl- quinolones (US 5,330,992), styryl compounds (US 5,217,999), styryl-substituted pyridyl compounds (US 5,302,606), selenoindoles and selenides (WO 94/03427), tricyclic polyhydroxy compounds (WO 92/21660) and benzylphosphonic acid compounds (WO 91/15495), pyrimidine derivatives (US 5,521, 184 and WO 99/03854), indolone derivatives and pyrrolo-substituted indolinones (US 5,792,783, EP 934 931, US 5,834,504, US 5,883,116, US 5,883,113, US 5,886,020, WO 96 / 40116 and WO 00/38519), as well as monocyclic, bicyclic bis and aryl heteroaryl compounds (EP 584,222, US 5,656,643 and WO 92/20642).. , quinazoline derivatives (EP 602,851, EP 520 722, US 3,772,295 and US 4,343,940) and aryl and heteroaryl quinazoline (US 5,721, 237, US 5,714,493, US 5,710,158 and WO 95/15758). However, none of these compounds have been described as potent and selective inhibitors of the c-kit or of the trajectory of the c-kit. With respect to our previous invention which is described in WO2004014903, we find that the compounds corresponding to the 2- (3-aminoaryl) amino-4-aryl-thiazoles are potent and selective inhibitors of the c-kit or of the path of the c-kit These compounds are good candidates for the treatment of diseases such as autoimmune diseases, inflammatory diseases, cancer and mastocytosis. We have now determined that other 2- (3-substituted-aryl) amino-4-aryl-thiazole derivatives display a very strong inhibitory activity in various forms of the c-kit. Therefore, the present invention discloses compounds belonging to 2- (3-ketoaryl) amino-4-aryl-thiazoles. These compounds are capable of selectively inhibiting signal transduction involving the tyrosine phosphokinase c-kit and its mutant forms. In a first embodiment, the invention is directed to compounds of formula I, which may represent either free base forms of pharmaceutically acceptable substances or salts thereof: FORMULA I and wherein R6 and R7 are independently selected from one of the following: i) hydrogen, a halogen (selected from F, Cl, Br or I), ii) an alkyl group defined as a linear, branched or cycloalkyl containing from 1 to 10 carbon atoms, or from 2 or 3 to 10 carbon atoms, (for example methyl, ethyl, propyl, butyl, pentyl, hexyl ...) and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen and nitrogen (the latter optionally in the form of a pendant basic nitrogen functionality); as well as trifluoromethyl, carboxyl, cyano, nitro, formyl; (iii) an aryl group defined as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as -halogen (selected from I, F, Cl or Br); - an alkyl group1; a cycloalkyl, aryl or heteroaryl group optionally substituted by a pendant basic nitrogen functionality; trifluoromethyl, O-alkyl1, carboxyl, cyano, nitro, formyl, hydroxy, NH-alkyl1, N (alk1) (aikyl1), and amino, the latter nitrogen substituents optionally in the form of a basic nitrogen functionality; (V) a heteroaryl group defined as a pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, dolyl, benzimidazole, quinolinyl group, which may additionally carry any combination, at any position on the ring, of one or more substituents such as -halogen (selected from F, Cl, Br or I); - an alkyl group1; - a cycloalkyl, aryl or heteroaryl group optionally substituted by a pendant basic nitrogen functionality, trifluoromethyl, O-alkyl1, carboxyl, cyano, nitro, formyl, hydroxy, NH-alkyl1, N (alkyl1) (alkyl1), and amino, last nitrogen substituents optionally in the form of a basic nitrogen functionality; (v) trifluoromethyl, carboxyl, cyano, nitro, formyl, hydroxy, N (alkyl) (alkyl), and amino, the latter nitrogen substituents optionally in the form of a basic nitrogen functionality. R8 is one of the following: (i) hydrogen, or (ii) a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, or (ii) CO-R8 or COOR8 or CONHR8 or SO2R8 wherein R8 can be - a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, or an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen (selected from F, Cl, Br or I), alkyl groups containing 1 to 10 atoms of carbon and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality; as well as trifluoromethyl, C? -6 alkyloxy, carboxyl, cyano, nitro, formyl, hydroxy, C? -6 alkylamino, C? -6 dialkylamino, and amino, the latter nitrogen substituents optionally in the form of a functionality of basic nitrogen pendant; as well as CO-R, COO-R, CONH-R, SO2-R and SO2NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with at least one heteroatom, notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, or - a heteroaryl group such as a pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, indolyl, benzimidazole, quinolinyl group, which can additionally carry any combination , at any position on the ring, of one or more substituents such as halogen (selected from F, Cl, Br or I), alkyl groups containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen ( selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality; as well as trifluoromethyl, C? -6 alkyloxy, carboxyl, cyano, nitro, formyl, hydroxy, C? -6 alkylamino, C1-6 dialkylamino, and amino, the latter optional nitrogen substituents in the form of a functional basic nitrogen; as well as CO-R, COO-R, CONH-R, SO2-R, and SO2NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with at least one heteroatom , notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality. R2, R3, R4 and R5 each independently is selected from hydrogen, halogen (selected from F, Cl, Br or I), a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality; as well as trifluoromethyl, C 1-6 alkyloxy, amino, C? -6 alkylamino, C? -6 dialkylamino, carboxyl, cyano, nitro, formyl, hydroxy, and CO-R, COO-R, CONH-R, SO2 -R and SO2NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with at least one heteroatom, notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, A is: CH2, O, S, SO2, CO, or COO, B is a bond or NH, NCH3, NR *, (CH2) n (n is 0, 1 or 2), O, S, SO2, CO or COO, B! is an eniace or NH, NCH3, NR *, (CH2) n (n is 0, 1 or 2), O, S, SO2, CO or COO, R * being an alkyl1, aryl1 or heteroaryl1 W is a bond or a linker selected from NH, NHCO, NHCOO, NHCONH, NHSO2, NHSO2NH, CO, CONH, COO, COCH2, (CH2) n (n is 0, 1 or 2), CH2-CO, CH2COO, CH2-NH, O, OCH2 , S, SO2, and SO2NH. R1 is: a) a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a basic nitrogen pendant; b) an aryl or heteroaryl group optionally substituted by an alkyl or aryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality c) an alkyl1, aryl1 or heteroaryl1 . It will be understood that a C1-C10 alkyl includes a methyl, ethyl, propyl, and a C2 to C4 alkyl or a C2 to C10 alkyl. For example, a subgroup of compounds may correspond to wherein R1, R4 and R6 have the meaning as defined above. It will be understood that ABB 'includes but is not limited to: CH2, CH2-CO, CH2-CO-CH2, CH2COO, CH2-CH2-CO, CH2-CH2-COO, CH2-NH, CH2-CH2-NH, CH2 -NH-CH2 or CH2-NH-CO or CH2-CO-NH. It will be understood that A-B-B 'also includes but is not limited to: CO-CH2, COO-CH2, CO-CH2-CH2, CO-NH, or CO-NH-CH2 as well as O-CH2. It will also be understood that HN in B or B 'can be NCH3. In formula I above, when W is different from a single bond, it will be understood that A may also be NH or NCH3. In the above formula, the following combinations are contemplated: R6 is (iv), R4 is H or CH3, A-B-B 'is CO-NH and R1 is as defined above. R6 is (iv), R4 is H or CH3, A-B-B 'is CH2-CO-NH and R1 is as defined above. R6 is (iv), R4 is H or CH3, A-B-B 'is CH2-CO and R1 is as defined above. R6 is (iv), R4 is H or CH3, A-B-B 'is CH2-NH-CO and R1 is as defined above. R6 is (iv), R4 is H or CH3, A-B-B 'is CH2-NH and R1 is as defined above. R6 is (iv), R4 is H or CH3, A-B-B 'is CH2 and R1 is as defined above. R6 is W- (iv), R4 is C2 alkyl, A-B-B 'is CO-NH and R1 is as defined above. R6 is (iv), R4 is C2 alkyl, A-B-B 'is CH2-CO-NH and R1 is as defined above. R6 is (iv), R4 is a C2 alkyl, A-B-B 'is CH2-CO- and R1 is as defined above. R6 is a pyridyl according to (v), R4 is a C2 alkyl, ABB 'is CO-NH, CH2-CO-NH, CH2-CO, CH2-NH, CH2-NH-CO and R1 is as is defined above. In the above combination, R1 may be an alkyl1. In the above combination, R1 can be an aryl1. In the above combination, R1 may be a heteroaryl1.

In a preferred embodiment, when ABB 'is CONH, the invention is directed to compounds of the following formula 1-1: wherein R is H or an organic group which may be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a basic nitrogen functionality pendant. In another preferred embodiment, the invention is directed to amide-aniline compounds of the following formula I-2: wherein R is H or an organic group which may be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with: - a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a basic nitrogen functionality pendant; - a SO2-R group in which R is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; - a group CO-R or CO-NRR ', wherein R and R' independently are chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I, Cl , Br and F, and / or carrying a pendant basic nitrogen functionality. Among the particular compounds in which R1 has the meaning as described above, the invention is directed to amide-benzylamine compounds of the following formula I-3: wherein R is H or an organic group which can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or an alkyl, cycloalkyl, aryl or heteroaryl group substituted by an alkyl, cycloaikyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a group -SO2-R wherein R is an alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are chosen from H or an aryl, heteroaryl, alkyl and cycloalkyl group optionally substituted with at least one heteroatom and / or carrying a functionality of basic nitrogen pendant. Among the particular compounds in which R1 has the meaning as described above, the invention is directed to amide-phenol compounds of the following formula I-4: wherein R is H or an organic group which can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; or an alkyl, cycloalkyl, aryl or heteroaryl group substituted by an alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; a group -SO2-R wherein R is an alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are chosen from H or an aryl, heteroaryl, alkyl and cycloalkyl group optionally substituted with at least one heteroatom and / or carrying a functionality of basic nitrogen pendant.

Among the compounds of formula I, the invention is particularly directed to 3- (thiazol-2-ylamino) -benzamide compounds of the following formula I-5: i-5 wherein Y is a straight or branched, straight-chain alkyl group containing from 1 to 10 carbon atoms, especially CH2 or CH2-CH2; or NH where Z represents an aryl or heteroaryl group, optionally substituted at one or more positions on the ring with any permutation of the following groups: a halogen such as F, Cl, Br, I; - a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom notably a halogen selected from I, Cl, Br and F and / or carrying a pendant basic nitrogen functionality; - an O-R, wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Ci, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an NRaRb, where Ra and Rb represent a hydrogen, or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a functionality or a hanging basic nitrogen cycle; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; R2 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, cyano or alkoxy; R3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, cyano or alkoxy; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, cyano or alkoxy; R5 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, cyano or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazoyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; and R7 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality. An example of preferred compounds of the above formula is described below: 001: 2-diethylamino-ethyl ester of 4-acid | -methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzoylamino-1-benzoic acid Among the compounds of the formula I, the invention is in particular incorporated by the compounds of the following formula II: wherein X is R or NRR ', and wherein R and R' independently are chosen from H, an aryl, a heteroaryl, an alkyl, or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally carrying a hanging basic nitrogen functionality; or an aryl, a heteroaryl, an alkyl or a cycloalkyl group substituted with an aryl, a heteroaryl, an alkyl or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally bearing a pendant basic nitrogen functionality, R 2 is hydrogen, halogen or a linear or branched alkyl group containing 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifiuoromethyl or alkoxy; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R5 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from i, Cl, Br and F, and / or carrying a hanging basic nitrogen functionality. In another alternative, the substituent R6, which in the formula II is connected to the 4-position of the thiazole ring, can instead occupy the 5-position of the thiazole ring. Among the preferred compounds corresponding to formulas I and II, the invention is directed to compounds in which R1 and X, respectively, are an alkyl, aryl or substituted heteroaryl group carrying a pendant basic nitrogen functionality represented by, for example, structures aam shown below, wherein the wavy line and the arrow line correspond to the point of attachment to the core structure of formula I or II. k m Among the groups a to f and g to m R1 of formula I and X of formula II is preferably group d. Also, for g a m, the arrow includes a point of attachment to the core structure via a phenyl group. In addition, among the compounds of the formula I or II, the invention concerns the compounds in which R2 and R3 are hydrogen. Preferably, R 4 is a methyl group and R 5 is H. In addition, R 6 is preferably a 3-pyridyl group (cf. later structure g), or a 4-pyridyl group (cf. later structure h). The wavy line in structure g and h corresponds to the point of attachment to the core structure of formula I or II. g n In this manner, the invention contemplates: 1. A compound of formula II as described above, wherein X is a group d and R6 is a 3-pyridyl group. 2. A compound of the formula II as described above, wherein X is the group d and R4 is a methyl group. 3. A compound of the formula I or II as described above, wherein R1 is the group d and R2 is H. 4. A compound of the formula I or II as described above, wherein R1 is the group d and R2 is H. 5. A compound of the formula I or II as described above, wherein R1 is the group d and R2 and / or R3 and / or R5 is H. 6. A compound of the formula I or II as described above, wherein R6 is a 3-pyridyl group and R3 is a methyl group. 7. A compound of the formula I or II as described above, wherein R6 is a 3-pyridyl group and R2 is H. 8. A compound of the formula I or II as described above, wherein R2 and / or R3 and / or R5 is H and R4 is a methyl group. 9. A compound of the formula I or II as described above, wherein R2 and / or R3 and / or R5 is H and R4 is a methyl group and R6 is a 3-pyridyl group. Among the compounds of the formula II, the invention is particularly comprised by the compounds wherein R2, R3, R5 are hydrogen, corresponding to the following formula 11-1: FORMULA i i-1 wherein X is R or NRR 'and wherein R and R' independently are chosen from H or an organic group which can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms; carbon optionally substituted with at least one hetero atom or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifiuoromethyl and axyloxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from l, Cl, Br and F, and / or carrying a hanging basic nitrogen functionality. In another alternative, the substituent R6, which in the formula II is connected to the 4-position of the thiazole ring, can instead occupy the 5-position of the thiazole ring.

EXAMPLES 002: N- (3,5-Bis-trifluoromethyl-phenol) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 1 H NMR (DMSO-d 6) d = 2.36 (s, 3 H, ArCH 3); 7.43 (d, 1 H, J = 7.5 Hz, Ar-H); 7.68 (dd, 1 H, J = 7.5, 1.5 Hz, Ar-H); 7.73 (s, 1 H, thiazole-H); 7.82 (m, 3H, pyridyl-H + Ar-H); 8.54 (m, 4H, pyridyl-H + 2xAr-H); 8.85 (br s, 1 H, Ar-H); 9.67 (s, 1 H, NH), 10.84 (s, 1 H, NH). 003: N- (3,5-bis-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 092: N-cyclohexyl-4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 1 H NMR (DMSO-d 6) d 1.00-1.40 (m, 5H, cyclo-H); 1.50-1.85 (m, 5H, Cyclo-H); 2.34 (s, 3H, ArCH3); 7.28 (d, 1 H, J = 7.9Hz, Ar-H); 7.48 (dd, 1 H, J = 7.9, 1.5 Hz, Ar-H); 7.67 (s, 1 H, thiazole-H); 7.82 (d, 2H, J = 6.0 Hz, pyridyl-H); 8.57 (d, 2H, J = 6.0Hz, pyridyl-H); 8.63 (d, 1H, J = 1.5 Hz, Ar-H); 9.55 (s, 1 H, NH). 093: 4-methyl-N- (1-methyl-1 H -indol-6-yl) -3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 094: N- (2-methoxy-ethyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 096: N- (2-cyano-ethyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide Among the compounds of the formula II, the invention is particularly comprised by the compounds wherein X is a substituted aryl group, corresponding to the N- [3- (lyozol-2-ylamino) -phenyl-amide family and the following formula II-3: FORMULA II-3 wherein Ra, Rb, Rc, Rd, Re are independently chosen from H or an organic group which may be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; a group -SO 2 -R wherein R is an alkyl, aryl cycloalkyl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are selected from H, an alkyl, a cycloalkyl, a heteroaryl group or arid, optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; Ra, Rb, Rc, Rd, Re can also be - a halogen such as I, Cl, Br and F - a group NRR 'wherein R and R' are H or an aikali iineai or branched group containing from 1 to 10 carbon atoms optionally substituted with at least one hetero atom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - an OR group where R is H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; a group -SO2-R 'wherein R' is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a group NRaCORb where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a group NRaCONRbRc where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or a heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a COOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a CONRaRb, where Ra and Rb are a hydrogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a nitrogen functionality basic pendant; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or a heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an NHCOOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group, optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an OSO2R, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an optionally substituted alkyl, a cycloalkyl, an aryl or heteroaryl group with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a NRaOSO2Rb where Ra and Rb are a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; Ra can also be a hydrogen; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from i, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a CN group - a trifluoromethyl group R4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heeroaryl group tai as a 2, 3, or 4-β-iridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a hanging basic nitrogen functionality.

EXAMPLES 028: N- (2-Fluoro-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 029: N- (3-Fluoro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylammon) -benzamide 030: 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -N- (3-trifluoromethyl-phenyl-benzamide 031: 4-methyl-N- (4-methyl-3-trifluoromethyl-phenyl) -3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 032: N- (2-fluoro-5-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 1 H NMR (DMSO-d 6) d = 2.39 (s, 3H, ArCH 3); 7.41 (d, 1 H, J = 7.9 Hz, Ar-H); 7.54-7.70 (m, 3H, Ar-H); 7.72 (s, 1 H, thiazole-H); 7.82 (d, 2H, J = 6.0Hz, pyridyl-H); 8.10 (dd, 1 H, J = 6.8, 2.2 Hz, Ar-H); 8.55 (d, 2H, J = 6.0 Hz, pyridyl-H); 8.84 (d, 1 H, J = 1.8 Hz, Ar-H); 9.65 (s, 1 H, NH); 10.31 (s, 1 H, NH). 033: N- (4-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 034: N- (4-fluoro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 035: N- (3-fluoro-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 036: N- (4-tert-butyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 038: N- (3-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 039: N- (3-cyano-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 1 H NMR (DMSO-d 6) d = 2.37 (s, 3 H, ArCH 3); 2.46 (s, 3H, ArCH3) 7.43 (m, 2H, Ar-H); 7.63 (dd, 1H, J = 7.9, 1.8 Hz, Ar-H); 7.72 (s, 1 H, thiazole-H); 7.83 (d, 2H, J = 6.0 Hz, pyridyl-H); 7.96 (dd, 1 H, J = 8.3, 1.8 Hz, Ar-H); 8.19 (d, 1 H, J = 2.3 Hz, Ar-H); 8.55 (d, 2H, J = 6.0Hz, pyridyl-H); 8.81 (d, 1 H, J = 1.5 Hz, Ar-H); 9.65 (s, 1 H, NH); 10.46 (s, 1 H, NH). 040: N- (3-bromo-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 041: N- (3-bromo-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 042: N- (3,5-dibromo-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 043: N- (3-chloro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 044: N- (3-chloro-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 045: N- (3-methoxy-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 046: 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -N-m-tolyl-benzamide 047: N- (4-fluoro-3-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 048: N- (3-vodo-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 049: 4-methyl-N- (3-nitro-phenyl) -3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 050: 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -N-p-tolyl-benzamide 051: 4-methyl-N-phenyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 052: N- (3,4-dimethyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 053: 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylammon) -N- (3-trifluoromethoxy-phenyl-benzamide) 054: N- (3,4-dicyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 055: N- (2-fluoro-5-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 056: N- (2,4-difluoro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide I r 057: N- (4-cyano-2-fluoro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 058: N- (2-fluoro-4-methyl-pheny1) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 059: N- (2,4-difluoro-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 060:. N- (4-cyano-2-fluoro-phenyl) -4-methyl-3- (4-pyridin-3-ii-thiazol-2-ylamino) -benzamide Benzamide 061: N- (2-fluoro-4-methyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 062: N- (4-cyano-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylammon) -benzamide 065: N- (4-fluoro-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 099: 4-Methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -N-m-tolyl-benzamide 100: 4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylammon) -N- (3-trifluoromethyl-phenyl) -benzamide 01: 4-methyl-N- (4-methyl-3-trifluoromethyl-pheyp-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 102: N- (2-fluoro-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 105: N- (4-cyano-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide 106: N- (4-cyano-3-methyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide Among the compounds of the formula II, the invention is particularly comprised of the compounds wherein X is a substituted aryl group, corresponding to the 4- (4-susyiuido-1-ylmethyl) -N- [3- (thiazol-2) family. -ylamino) -phenyl] -benzamide and the following formula II-4: FORMULA II-4 wherein X is a heteroatom, such as O or N; wherein Ra, Rb, Rd, Re, Rf, Rg, Rh are independently chosen from H or an organic group which may be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRR 'wherein R and R' are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted by at least one heteroaryme and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from i, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or an OR group where R is H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; a group -SO2-R 'wherein R' is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRaCORb where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRaCONRbRc where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a COOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from i, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a CONRaRb, where Ra and Rb are a hydrogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a functionality of basic nitrogen pendant; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or an NHCOOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heieroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or an OSO2R, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a NRaOSO2Rb where Ra and Rb are a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; Ra can also be a hydrogen; a cycloalkyl, an aryl or a heteroaryl group optionally substituted with at least one heteroamino, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a group -SO2-R wherein R is an aiquiio, aryl cycloalkyl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I , Cl, Br and F, and / or carrying a hanging basic nitrogen functionality. Ra, Rb, Rd, Re can also be halogen such as Cl, F, Br,. I or trifluoromethyl; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heeroaryl group such as a 2, 3, or 4-pyridyl group, which 0 may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazoyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen, an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (V) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group which confers one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a hanging basic nitrogen functionality.

EXAMPLES 004: 4-methyl-N-r4- (4-methyl-piperazin-1-ylmethyl) -3-trifluoromethyl-phen.p-3- (4-pyridin-4-yl-thiazol-2-ylamino) - benzamide 1 H NMR (MeOH-d 4) d = 2.41 (s, 6H, NCH 3 + ArCH 3); 2.50-2.70 (m, 4H, piperazine-H); 2.90 (m, 4H, piperazine-H); 3.68 (br s, 2H, CH2-piperazine); 7.38 (d, 1H, J = 7.9 Hz, Ar-H); 7.50 (m, 1 H, thiazole-H); 7.60 (m, 1 H, Ar-H); 7.76 (d, 1 H, J = 8.3 Hz, Ar-H); 7.90 (m, 2H, pyridyl-H); 8.00 (m, 1 H, Ar-H); 8. 12 (m, 1 H, Ar-H); 8.46 (m, 2H, pyridyl-H); 8.90 (m, 1H, Ar-H). 005: 4-methyl-N- (4-ri- (4-methyl-piperazin-1-yl) -etin-phenyl) -3- (4-pyridin-3-yl-thiazole-2) -lamino) -benzamida Among the compounds of the formula II, the invention is particularly comprised of the compounds wherein X is a group substituted with aryl, corresponding to the family of 3-disubstituted-amino-N- [3- (thiazol-2-ylamino) - phenyl] -benzamide and the following formula 11-5: FORMULA H-5 wherein Ra, Rb, Rc, Re, Rf, Rg, are independently chosen from H or an organic group which can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one hetero atom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRR 'wherein R and R' are H or a linear or branched alkyl group having from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from 1, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or an OR group where R is H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from i, Cl, Br and F or carrying a pendant basic nitrogen functionality; a group -SO2-R 'wherein R' is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRaCORb where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from l, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a group NRaCONRbRc where Ra and Rb are H or a branched or iineal aiquiio group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkio, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - or a COOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a CONRaRb, where Ra and Rb are a hydrogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a functionality of basic nitrogen pendant; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or an NHCOOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group, optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an OSO2R, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkio, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a NRaOSO2Rb where Ra and Rb are a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; Ra can also be a hydrogen; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - or a group -SO2-R wherein R is an alkyl, cycloalkyl, aryl Or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are chosen from H, an alkyl, a cycloalkio, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I , Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; Ra, Rb, Rc, Re can also be halogen such as Cl, F, Br, 1 or trifluoromethyl; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group containing 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched aiquiio group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a hanging basic nitrogen functionality.

EXAMPLES 089: N- (3-d.methylamino-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 1 H NMR (DMSO-d 6) d = 2.36 (s, 3 H, ArCH 3); 2.88 (s, 6H, 2xCH3); 6.50 (d, 1 H, J = 7.9 Hz, Ar-H); 7.10-7.30 (m, 3H, Ar-H); 7.38 (d, 1H, J = 7.9 Hz, Ar-H); 7.62 (dd, 1 H, J = 7.9, 1.5 Hz, Ar-H); 7.70 (s, 1 H, thiazole-H); 7.85 (d, 2H, J = 6.4Hz, pyridyl-H); 8.54 (d, 1 H, J = 6.4 Hz, pyridyl-H); 8.78 (br s, 1 H, Ar-H); 9.63 (s, 1 H, NH), 10.04 (s, 1 H, NH). 090: N- (3-dimethylamino-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide In a second embodiment, the invention is directed to a process for the manufacture of a compound of the formula I described above. This causes the condensation of a substrate of the general formula 10 with a thiourea of type 11. l to 10 The substituent "L" in formula 10 is a nucleofugic leaving group in the nucleophilic substitution reactions (for example, L can be selected from chlorine, bromine, iodine, toluenesulfonyloxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, etc., with L being preferably a group bromine). The group R1 in the formula 11a corresponds to an alkoxy group. The reaction of 10 with 1 a-d leads to a thiazole-type product of the formula 12a-d.

Formula 12a is the same as formula I. Therefore, R1 in 12a corresponds to R1 in formula I.

Examples of synthesis of the compound General: all the chemicals used are commercial reactive grade products. Dimethylformamide (DMF), methanol (MeOH) are commercial grade anhydrous and are used without further purification. Dichloromethane and tetrahydrofuran (THF) are freshly distilled under a stream of argon before being used. The progress of the reactions is monitored by thin layer chromatography using pre-coated silica gel 60F 254, Fluka TLC plates, which are visualized under UV light. Multiplicities in the 1 H NMR spectrum are indicated as singlet (s), broad singlet (br s), doublet (d), triplet (t) :, quadruplet (q), and multiplet (m) and the NMR spectrum are analyzed in a 300MHz Broker spectrometer. 4-bromoacetyl-pyridine, HBr salt Dibromine (17.2 g, 108 mmol) is added dropwise to a cold (0 ° C) solution of 4-acetyl-pyridine (12 g, 99 mmol) in acetic acid containing 33% HBr (165 ml) under stirring vigoroza The stirred mixture is heated vigorously at 40 ° C for 2 hours and then at 75 ° C. After 2 hours at 75 ° C, the mixture is cooled and diluted with ether (400 ml) to precipitate the product, which is recovered by filtration and washed with ether and acetone to give white crystals (100%). This material can be recrystallized from methanol and ether. 1 H NMR (DMSO-d 6) d = 5.09 (s, 2H, CH 2 Br); 8.62 (m, 2H, pyridyl-H); 9.07 (m, 2H, pyridyl-H). 4-Methyl-3-thioureido-benzoic acid methyl ester Benzoyl chloride (5.64 g, 80 mmol) is added dropwise to a well-stirred solution of ammonium thiocyanate (3.54 g, 88 mmol) in acetone (50 ml). The mixture is refluxed for 15 minutes, then the 3-amino-4-methyl-benzoic acid methyl ester (13.2 g, 80 mmol) is slowly added portionwise. After 1 h, the reaction mixture is poured into water (350 ml) and the bright yellow precipitate is isolated by filtration. This crude solid is stirred at room temperature with an excess of anhydrous potassium carbonate in 200 ml of methanol for 2 hours. Then, the solvent is removed under reduced pressure and the crude product is extracted with ethyl acetate and washed with water. Dry the organic layer over Na2SO and concentrate to give a white solid. The solid is stirred in ether for 15 minutes and filtered to provide the final product as a white solid. 1 H NMR (DMSO-d 6) d = 2.22 (s, 3H, ArCH 3); 3.81 (s, 3H, CO2CH3); 7.38 (d, 1 H, J = 7.9 Hz, Ar-H); 7.70 (dd, 1 H, J = 7.9, 1.5 Hz, Ar-H); 7.82 (d, 1 H, J = 1.8 Hz, Ar-H). 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzoic acid methyl ester A mixture of 4-bromoacetyl-pyridine, HBr salt (0.40 g, 1.43 mmol), 4-methyl-3-thioureido-benzoic acid ethyl ester (0.32 g, 1.43 mmol) and KHCO3 (-0.4 g) in ethanol (10 g. ml) is heated at 75 ° C for 20 h. The mixture is cooled, filtered (KHCO3 removal) and evaporated under reduced pressure.

The residue is dissolved in CHCl3 (40 ml) and washed with saturated aqueous sodium acid carbonate solution and with water. The organic layer is dried over Na2SO4 and concentrated. The crude product is triturated in small amounts of ethyl acetate and filtered to provide the final product as an orange solid. 1 H NMR (DMSO-d 6) d = 2.38 (s, 3H, ArCH 3); 3.88 (s, 3H, CO2CH3); 7.58 (dd, 1H, J = 7.9, 1.8 Hz, Ar-H); 7.75 (s, 1 H, thiazole-H); 7.85 (d, 2H, J = 6.0Hz, pyridyl-H); 8.62 (d, 1 H, J = 6.0 Hz, pyridyl-H); 9.12 (d, 1 H, J = 1.8 Hz, Ar-H); 9.63 (s, 1 H, NH).

N- (4-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzoic acid methyl ester A 2M solution of trimethyl aluminum in hexane (1.9 ml) is added dropwise to a cold (0 ° C) solution of 4-amino-benzonitrile (0.29 g, 2. 46 mmol) in anhydrous dichloromethane (30 ml) under argon atmosphere. The mixture is warmed to room temperature and stirred at room temperature for 30 minutes. A solution of 4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzoic acid methyl ester (0.80 g, 2.46 mmol) in anhydrous dichloromethane (30 ml) is added slowly, and The resulting mixture is refluxed for 5 hours. The mixture is cooled to 0 ° C and quenched by the dropwise addition of a 4N aqueous sodium hydroxide solution (3 ml). The mixture is extracted with dichloromethane (3x20 ml). The combined organic layers are washed with brine (3x20 ml) and dried over anhydrous MgSO 4. N- (4-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide is obtained in 98% after trituration of the crude product in methanol 1 H NMR (CDC 3) d = 2.40 (s, 3 H, ArCH 3); 7.40 (d, 1 H, J = 7.9Hz, Ar-H); 7.63 (dd, 1 H, J = 7.9, 1.5 Hz, Ar-H); 7.72 (s, 1 H, thiazole-H); 7.80-7.88 (m, 4H, Ar-H); 8.10 (d, 2H, J = 8.6Hz, Ar-H); 8.56 (m, 2H, Ar-H); 8.86 (d, 1 H, J = 1.8 Hz, Ar-H); 9.66 (br s, 1 H, NH).

EXAMPLES In a third embodiment, the invention describes a pharmaceutical composition comprising a compound as described above. Said medicament may take the form of a pharmaceutical composition adapted for oral administration, which may be formulated using pharmaceutically acceptable carriers well known in the art in suitable dosages. Such carriers allow the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, serums, slurries, suspensions, and the like, for ingestion by the patient. In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries that facilitate the processing of the active compounds into preparations that can be used pharmaceutically. Additional details on the techniques for formulation and administration can be found in the latest edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa). The composition of the invention may also take the form of a pharmaceutical or cosmetic composition for topical administration. Said compositions may be present in the form of a gel, paste, ointment, cream, lotion, aqueous solutions in liquid, aqueous-alcoholic or oily suspension, or dispersions of the lotion or serum type, or anhydrous or lipophilic gels, or emulsions of liquid or semi-solid consistency of the milky type, obtained by the dispersion of a fatty phase in an aqueous phase or vice versa, or of suspensions or emulsions of soft, semi-solid consistency of the cream or gel type, or alternatively of microemulsions, of microcapsules , of microparticles or vesicular dispersions for the ionic and / or nonionic type. These compositions are prepared according to standard methods. The composition according to the invention comprises any ingredient commonly used in dermatology and cosmetics. It may comprise by at least one ingredient selected from hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, emollients, viscosity enhancing polymers, humectants, surfactants, preservatives, antioxidants, solvents and fillers, antioxidants, solvents, perfumes , fillers, depuration agents, bactericides, odor absorbers and coloring matter. As the oils that may be used in the invention, there may be mentioned mineral oils (liquid paraffin), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils, synthetic oils, silicone oils (cyclomethicone) and oils fluorinated Fatty alcohols, fatty acids (stearic acid) and waxes (paraffin, carnauba, beeswax) can also be used as fatty substances. As emulsifiers which can be used in the invention, there are contemplated glycerol stearate, polysorbate 60 and a mixture of PEG-6 / PEG-32 / glycol stearate. As hydrophilic gelling agents, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural clays and gums, and as lipophilic gelling agents, there may be mentioned modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, or alternatively ethylcellulose and polyethylene. As hydrophilic active agents, proteins or hydrolysates of proteins, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, vitamins, starch and plant extracts, in particular those of Aloe vera, can be used. As lipophilic active agents, retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, can be used, ceramides and essential oils. These agents help the extra moisture or softening aspects of the skin when they are used. In addition, a surfactant may be included in the composition so as to provide deeper penetration of the compound capable of reducing mast cells, such as a tyrosine kinase inhibitor, preferably a c-kit inhibitor. Among the contemplated ingredients, the invention comprises penetration enhancing agents selected for example from the group consisting of mineral oil, water, ethanol, triacetin, glycerin and propylene glycol; Cohesion agents selected for example from the group consisting of polyisobutylene, polyvinyl acetate and polyvinyl alcohol, and thickening agents. Chemical methods of enhancing topical absorption of drugs are well known in the art. For example, compounds with penetration enhancing properties include sodium lauryl sulfate (Dugard, PH and Sheuplein, RJ, "Effects of lonic Surfactants on the Permeabiiity of Human Epidermis: An Electromeíric Síudy," J. Ivesí, Dermaíol., V 60, pp. 263-69, 1973), lauri oxide! amine (Johnson et al., US 4,411, 893), azone (Rajadhyaksha, US 4,405,616 and 3,989,816) and decylmethyl sulfoxide (Sekura, DL and Scala, J., "The Percutaneous Absorption of Alkylmethyl Sulfides' Pharmacology of the Skin, Advances In Biolocy of Skin, (Appleton-Century Craft) V. 12, pp. 257-69, 1972. It has been observed that the increase of the polarity of the main group in amphoteric molecules increases their properties of penetration intensification but at the expense of increase their skin irritation properties (Cooper, ER and Berner, B., "Interaction of Surfactants with Epidermal Tissues: Physiochemical Aspects," Surfactant Science Series, V. 16, Reiger, MM ed. (Marcel Dekker, Inc.) pp. 195-210, 1987.) A second class of chemical enhancers are generally referred to as co-solvents.These materials are relatively easily absorbed relatively easily, and, through a variety of mechanisms, they perform enhanced permeation for some Ethanol (Gale et al., U.S. Pat. No. 4,615,699 and Campbell et al., U.S. Pat. Nos. 4,460,372 and 4,379,454), dimethyl sulfoxide (US 3,740,420 and 3,743,727, and US 4,575,515), and glycerin derivatives (US 4,322,433) are some examples of compounds that have shown an ability to increase the absorption of various compounds. The pharmaceutical compositions of the invention are also intended to be used in administration with aerosolized formulation to target areas of a respiratory tract of the patient. Devices and methodologies for the release of the aerosolized discharge of a drug formulation are described in US 5,906,202. The formulations are preferably solutions, for example, aqueous solutions, ethanolic solutions, aqueous / ethanolic solutions, saline solutions, colloidal suspensions and microcrystalline suspensions. For example, aerosolized particles comprise the aforementioned active ingredient and a carrier (e.g., a drug and pharmaceutically active respiratory carrier) that is formed by forcing the formulation through a nozzle, this nozzle preferably being in the form of a porous membrane flexible. The particles have a size that is sufficiently small that when the particles are formed, they are suspended in the air for a sufficient amount of time such that the patient can inhale the particles into the patient's lungs. The invention includes the systems described in US 5,556,611: - liquid-gas systems (a liquefied gas is used as a propellant gas (e.g., low boiling FCHC or propane, butane) in a pressure vessel, - suspension aerosol ( the active substance is suspended in solid form in the liquid propulsive phase), - pressurized gas system (a compressed gas such as nitrogen, carbon dioxide, dinitrogen monoxide, air is used.) Thus, according to the invention The pharmaceutical preparation is made in that the active substance is dissolved or dispersed in a suitable non-toxic medium and said solution or dispersion is sprayed for an aerosol, that is, it is extremely finely distributed in a carrier gas. example in the form of aerosol propellant gas packages, pump aerosols or other devices known per se for fogging liquid and atomization solid that in particular they allow an exact individual dosage. Thus, the invention is also directed to aerosol devices comprising the compound as defined above and said formulation, preferably with metered dose valves. The pharmaceutical compositions of the invention are also intended to be used for intranasal administration. In this regard, pharmaceutically acceptable carriers for the administration of the compound to nasal mucosal surfaces will be readily appreciated by the ordinary artisan. These carriers are described in "Remington's Pharmaceutical Sciences" 16th edition, 1980, Ed. By Arthur Osol, the disclosure of which is incorporated herein by reference. The selection of appropriate carriers depends on the particular type of administration contemplated. For administration via the upper respiratory touch, the composition can be formulated in a solution, for example, water or isotonic saline, pH regulated or unregulated pH or as a suspension, for intranasal administration as drops or as an aerosol . Preferably, such solutions or suspensions are isotonic relative to nasal secretions and near the same pH, ranging, for example, from about pH 4.0 to about pH 7.4, pH 6.0 to pH 7.0. The pH regulators must be physiologically compatible and include, simply by way of example, phosphate pH regulators. For example, a representative nasal decongestant is described as being pH regulated at a pH of about 6.2 (Remington's, Id on page 1445). Of course, the ordinary artisan can easily determine an adequate salt content and pH for a harmless aqueous carrier for upper and / or nasal respiratory administration. Common intranasal carriers include gels, creams, pastes or nasal ointments with a viscosity of, for example, from about 10 to about 3000 cps, or from about 2500 to 6500 cps, or greater, can also be used to provide a more maintained contact with nasal mucosal surfaces. Such carrier viscous formulations can be based on, simply by way of example, alkylcelluloses and / or other biocompatible carriers of high viscosity well known in the art (see for example, Remington's, cited supra). A preferred alkyl cellulose is, for example, methylcellulose in a concentration ranging from about 5 to about 1000 or more mg per 100 ml carrier. A more preferred concentration of methylcellulose is, simply by way of example, from about 25 to about mg per 100 ml of carrier. Other ingredients, such as preservatives, colorants, lubricants or viscous mineral or vegetable oils, perfumes, extracts of natural or synthetic pineapples iaies such as aromatic oils, and viscosity enhancers and humectants such as, for example, glycerol, known in the art, are They can include to provide additional viscosity, moisture retention and pleasant texture and odor for the formulation. For nasal administration of solutions or suspensions according to the invention, various devices are available in the art for the generation of droplets, droplets and aerosols. A pre-measured unit dosage dispenser including a dropper or aerosol device containing a solution or suspension for release as drops or as an aerosol is prepared containing one or more doses of the drug to be administered and is another object of the invention. The invention also includes equipment containing one or more dehydrated unit doses of the compound, together with any of the required salts and / or pH regulating agents, preservatives, colorants and the like, ready for the preparation of a solution or suspension by the adding an adequate amount of water. Another aspect of the invention is directed to the use of said compound for the manufacture of a medicament. In other words, the invention comprises a method for the treatment of a disease related to unregulated c-kit transduction comprising the administration of an effective amount of a compound as defined above to a mammal in need of such treatment. More particularly, the invention is directed to a method for the treatment of a disease selected from autoimmune diseases, allergic diseases, bone loss, cancers such as leukemia and GIST, tumor angiogenesis, inflammatory diseases, inflammatory bowel diseases (IBD), intersficial cystitis, mastocytosis, infectious diseases, metabolic disorders, fibrosis, diabetes and CNS disorders comprising administering an effective amount of a compound described above to a mammal in need of such treatment. The compounds described above are useful for the manufacture of a medicament for the treatment of diseases related to unregulated c-kit transduction, including but not limited to: neoplastic diseases such as mastocytosis, canine mastocytoma, human gastrointestinal stromal tumor ( "GIST"), small cell lung cancer, non-small cell lung cancer, acute myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, colorectal carcinomas, gastric carcinomas, gastrointestinal stomal tumors, testicular cancers, glioblastomas, solid tumors and astrocytomas, - tumor angiogenesis, - metabolic diseases such as diabetes mellitus and its chronic complications; obesity; type II diabetes; hyperlipidemias and dyslipidemias; atherosclerosis; hypertension; and cardiovascular diseases, - Anergic pains such as asthma, allergic rhinitis, allergic sinusitis, anaphylactic syndrome, urticaria, angioedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis and skin inflammation due to insect bites and parasitic infestation of blood suction, - interstitial cystitis, - bone loss (osteoporosis), - inflammatory diseases such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions, - autoimmune diseases such as multiple sclerosis, psoriasis, inflammatory disease of the bowel, ulcerative colitis, Crohn's disease, rheumatoid arthritis and polyarthritis, local and systematic scleroderma, systemic lupus erythematosus, discoid lupus erythematosus, cutaneous lupus, dermatomyositis, polymyositis, Sjogren's syndrome, panarteritis nodosa, autoimmune enteropathy, as well as glomerulone proliferative effusions, graft-versus-host disease or graft rejection in any organ transplantation including kidney, pancreas, liver, heart, lung, and bone marrow, - other autoimmune diseases comprised by the Prevention are chronic active hepatitis and chronic fatigue syndrome, - disorders that cause subepidermal blisters such as pemphigus, - vasculitis, - diseases associated with melanocyte dysfunction such as hypermelanosis that results from melanocyte dysfunction and that includes lentigines, solar lentigo and senile, Dubreuilh melanosis, moles as well as malignant melanomas. In this regard, the invention comprises the use of compounds defined above for the manufacture of a medicament or a cosmetic composition for the bleaching of human skin, - CNS disorders such as psychiatric disorders, migraine, pain, memory loss and cell degeneration. Nervous More particularly, the method according to the invention is useful for the treatment of the following diseases: Depression which includes dysthymic disorder, cyclothymic disorder, bipolar depression, "melancholic" or severe depression, atypical depression, refractory depression, stationary depression, anorexia , bulimia, premenstrual syndrome, post-menopausal syndrome, other syndromes such as mental retardation and loss of concentration, pessimistic anxiety, agitation, self-deprecation, decreased libido, pain that includes, acute pain, postoperative pain, chronic pain, nociceptive pain, pain cancer, neuropathic pain, psychogenic pain syndromes, anxiety disorders including anxiety associated with hyperventilation and cardiac arrhythmias, phobic disorders, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, psychiatric emergencies such as panic attacks , which include psychosis, hallucinatory disorder, conversion disorders, phobias, mania, delirium, dissociative episodes including dissociative amnesia, dissociative fugue, and dissociative identity disorder, depersonalization, catatonia, stroke, severe psychiatric emergencies involving suicidal behavior, self -bandon, violent or aggressive behavior, trauma, borderline personality, and acute psychosis, schizophrenia including paranoid schizophrenia, disorganized schizophrenia, catatonic schizophrenia, and undifferentiated schizophrenia, - neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease , prion diseases, motor neuroma disease (AND), and amyotrophic lateral sclerosis (ALS), - disorders by the use of substances as referred to herein include but are not limited to drug addiction, drug abuse, drug habituation, drug dependence, withdrawal syndrome o and overdose, - cerebral ischemia - fibrosis - Duchenne muscular dystrophy. With respect to mastocytosis, the invention contemplates the use of the compounds as defined above for the treatment of different categories that can be classified as follows: Category I is composed of two sub-categories (IA and IB). Category IA is made by diseases in which the infiltration of masocytes is strictly localized in the skin. This category represents the most frequent form of the disease and includes: i) pigeon-like urticaria, the most common form of cutaneous mastocytosis, found particularly in children, ii) diffuse cutaneous mastocytosis, iii) solitary mastocytoma and iv) some rare subtypes similar to bullous, erythrodermic and telangiectatic mastocytosis. These forms are characterized by their excellent prognosis with spontaneous remissions in children and a very painless stage in adults. The short-term survival of this disease, in general, is comparable to that of the normal population and the translation in another form of rare mastocytosis. Category IB is represented by painless systemic disease (MS) with or without cutaneous involvement. These forms are much more common in adults than in children. The course of the disease is sometimes painless, but some signs of aggressive or malignant mastocytosis can occur, leading to poor function of the progressively damaged organ. Category II includes mastocytosis with an associated hematoc disorder, such as a myeloproliferative or myelodysplastic syndrome, or acute leukemia. These malignant mastocytosis usually does not involve the skin. The progression of the disease depends in general on the type of associated hematocal disorder that conditions the prognosis. Category III is represented by aggressive systemic mastocytosis in which massive infiltration of multiple organs by abnormal mastocytes is common. In patients who aspire to this type of aggressive clinical course, the peripheral blood aspects indicative of a rpieloproliferative disorder are more prominent. The progression of the disease can be very rapid, similar to acute leukemia, or some patients may show a longer survival time. Finally, category IV mastocytosis includes mast cell leukemia, characterized by the presence of mast cells circulating and piogenitors of mast cells that represent more than 10% of white blood cells. This entity probably represents the rarest form of leukemia in humans, and has a very poor prognosis, similar to the variant of rapid progression of malignant mastocytosis. Mast cell leukemia can occur either de novo or as the terminal phase of urticaria pigmentosa or systemic mastocytosis. The invention also contemplates the method as described for the treatment of recurrent bacterial infections, infections that re-emerge after asymptomatic periods such as bacterial cystitis. More particularly, the invention can be practiced for the treatment of bacterial infections expressing FimH, such as the Gram-negative enterobacteria which includes E. coli, Klebsiella pneumoniae, Serratia marcescens, Citrobactor freudii and Salmonella typhimurtum. In this method for the treatment of bacterial infection, the separate, sequential or concentrated administration of at least one antibiotic selected from bacitracin, cephalosporins, penicillins, aminoglycosides, tetracyclines, streptomycins and macrolide antibiotics such as erythromycin, the fluoroquinolones, actinomycin, the sulíonarnidas and trimeíoprima, are of interest. In a preferred embodiment, the invention is directed to a method for the treatment of neoplastic diseases such as mastocytosis, canine mastocytoma, human gastrointestinal stromal tumor ("GIST"), small cell lung cancer, non-small cell lung cancer, acute myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myenous myenous, colorectal carcinomas, gastric carcinomas, gastrointestinal stomal tumors, testicular cancers, glioblastomas, solid tumors and astrocytomas comprising the administration of a compound as defined herein to a human or mammal , especially dogs and cats, in need of it. In another preferred embodiment, the invention is directed to a method for the treatment of allergic diseases such as asthma, allergic rhinitis, allergic sinusitis, anaphylactic syndrome, urticaria, angioedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis and inflammation of the skin by insect bites and parasitic infestation of blood suction, comprising the administration of a compound such as it defines here a human or mammal, especially dogs and cats, in need of such treatment. In yet another preferred embodiment, the invention is directed to a method for the treatment of inflammatory diseases such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions comprising the administration of a compound as defined herein to a human in need of such treatment. In yet another preferred embodiment, the invention is directed to a method for the treatment of autoimmune diseases such as multiple sclerosis, psoriasis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, rheumatoid arthritis and polyarthritis, local and systematic scleroderma, lupus erythematosus systemic, discoid lupus erythematosus, cutaneous lupus, dermatomyositis, polymyositis, Sjogren's syndrome, panarteritis nodosa, autoimmune enteropathy, as well as proliferative glomerulonephritis comprising the administration of a compound as defined herein to a human in need of such treatment. In yet another preferred embodiment, the invention is directed to a method for the treatment of graft-versus-host disease or graft rejection in any organ transplantation that includes kidney, pancreas, liver, heart, lung, and bone marrow comprising administration of a compound as defined herein to a human in need of such treatment.

EXAMPLE 1 In Vitro TK Inhibition Assays Procedure Experiments are performed using purified intracellular domain of c-kit expressed in baculovirus. The estimation of kinase activity is assessed by tyrosine phosphorylation containing the target peptide estimated by the established ELISA assay.

Experimental results in tested compounds The result in Table 1 shows the potent inhibitory action of the catalytic activity of c-kit with an IC50 < 10 μM. Additional experiments (not shown) indicate that at least one compound acts as perfect competitive inhibitors of ATP.

EXAMPLE 2 Ex vivo TK inhibition assays Procedures Test of WT c-kit and mutated c-kit (JM) Proliferation assays The cells were run twice in PBS before co-firing 5 x 104 cells per well in 96-well plates in triplicate and stimulated with or without hematopoietic growth factors (HGF). After 2 days of culture, 37 Bq (1.78 Tbq / mmol) of [3 H] thymidine (Amersham Life Science, UK) are added for 6 hours. The cells are harvested and filtered through glass fiber filters and the incorporation of [3 H] thymidine in a scintillation counter is measured. For the proliferation assay all drugs are prepared as 20 mM stock solutions in DMSO and stored at -80 ° C. Fresh dilutions are made before each experiment. The drugs dissolved in DMSO are added at the start of the culture. The control cultures are made with corresponding dilutions of DMSO. The results are represented in percentages by taking proliferation without inhibitor as 100%.

Cells The human kit and murine Ba / F3 kit, the Ba / F3 mkitD27 (juxtamembrane deletion) is derived from the murine lL-3 dependent lymphoid cells proB Ba / F3. The FMA3 and P815 cell lines are mastocytoma cells that express endogenous mutated forms of Kit, ie, the deletion of the structure in the murine juxtamembrane coding region of codons from the 573 to 579 receptor. The MC-leukemic MC-line HMC-1 human expresses JM-V560G mutations.

Immunoprecipitation assays and western blotting analysis For each assay, 5,106 Ba / F3 cells and cells derived from Ba / F3 with several c-kit mutations are lysed and immunoprecipitated as described (Beslu et al., 1996), except that the cells are stimulated with 250 ng / ml of mKL. The cell lysates are immunoprecipitated with an anti-murine KIT of rabbit immune serum, directed against the cytoplasmic domain of KIT (Rottapel et al., 1991). Western blotting is hybridized with either anti-phosphotyrosine 4G10 antibody (UBI) or with anti-murine KIT immune to rabbit serum or with different antibodies (described in the antibody paragraph). The membrane is then incubated either with goat anti-mouse IgG antibody conjugated with HRP or with goat anti-rabbit IgG antibody conjugated with HRP (Immunotech). The proteins of interest are then visualized by incubation with ECL reagent (Amersham).

Experimental results The experimental results for several compounds according to the invention using the protocols described above are shown in Table 1: TABLE 1

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A compound of the formula 1

FORMULA? wherein R6 and R7 are independently from each other selected from one of the following: i) hydrogen, a halogen (selected from F, Cl, Br or I), ii) an alkyl group defined as a linear, branched or cycloalkyl group containing from 1 to 10 carbon atoms, or from 2 or 3 to 10 carbon atoms, (for example methyl, ethyl, propyl, butyl, pentyl, hexyl ...) and optionally substituted with one or more heteroatoms such as halogen (selected of F, Cl, Br or I), oxygen and nitrogen (the latter optionally in the form of a pendant basic nitrogen functionality); as well as trifluoromethyl, carboxyl, cyano, nitro, formyl; (iii) an aryl group defined as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as -halogen (selected from I, F, Cl or Br); - an alkyl group1; a cycloalkyl, aryl or heteroaryl group optionally substituted by a pendant basic nitrogen functionality; trifluoromethyl, O-alkyl1, carboxyl, cyano, nitro, formyl, hydroxy, NH-alkyl1, N (alkyl1) (alkyl1), and amino, the latter nitrogen substituents optionally in the form of a basic nitrogen functionality; (V) a heteroaryl group defined as a pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, dolyl, benzimidazole, quinolinyl group, which may additionally carry any combination, at any position on the ring, of one or more substituents such as -halogen (selected from F, Cl, Br or i); - a group aiquiio1; - a cycloalkyl, aryl or heteroaryl group optionally substituted by a pendant basic nitrogen functionality, trifluoromethyl, O-alkyl, carboxyl, cyano, nitro, formyl, hydroxy, NH-alkyl, N (alkyl) (alkyl), and amino, the last nitrogen substituents optionally in the form of a basic nitrogen functionality; (v) trifluoromethyl, carboxyl, cyano, nitro, formyl, hydroxy, N (alkyl) (alkyl), and amino, the latter nitrogen substituents optionally in the form of a basic nitrogen functionality. R8 is one of the following: (i) hydrogen, or (ii) a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, or (iii) CO-R8 or COOR8 or CONHR8 or SO2R8 wherein R8 can be - a linear or branched alkyl group containing 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, this latter optionally in the form of a pendant basic nitrogen functionality, or - an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen (selected from F, Cl, Br or I), alkyl groups containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality; as well as trifluoromethyl, C? -6 alkyloxy, carboxyl, cyano, nitro, formyl, hydroxy, C-? -6 alkylamino, C1-6 dialkylamino, and amino, the latter nitrogen substituents optionally in the form of a functionality of basic nitrogen pendant; as well as CO-R, COO-R, CONH-R, SO2-R and SO2NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with at least one heteroatom, notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, or - a heteroaryl group such as a pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, thiazolyl, imidazolyl group, pyrazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, indolyl, benzimidazole, quinolinyl, which can additionally carry any combination, at any position on the ring, of one or more substituents such as halogen (selected from F, Cl, Br or I), alkyl groups containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a basic nitrogen functionality pendant; as well as trifluoromethyl, C 1-6 alkyloxy, carboxyl, cyano, nitro, formyl, hydroxy, C 1-6 alkylamino, C 1-6 dialkylamino, and amino, the latter nitrogen substituents optionally in the form of a basic nitrogen functionality; as well as CO-R, COO-R, CONH-R, SO2-R, and SO2NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted by ?? minus one heteroatom, notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality. R2, R3, R4 and R5 each independently is selected from hydrogen, halogen (selected from F, Cl, Br or I), a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with one or more heteroatoms such as halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality; as well as trifluoromethyl, C-? 6 alkyloxy, amino, C? -6 alkylamino, C?? 6 dialkylamino, carboxyl, cyano, nitro, formyl, hydroxy, and CO-R, COO-R, CONH- R, S02-R and S02NH-R wherein R is a linear or branched alkyl group containing from 1 to 10 carbon atoms and optionally substituted with at least one heteroatom, notably a halogen (selected from F, Cl, Br or I), oxygen, and nitrogen, the latter optionally in the form of a pendant basic nitrogen functionality, A is: CH2, O, S, S02, CO, or COO, B is a bond or NH, NCH3, NR *, (CH2) n (n is 0, 1 or 2), O, S, S02, CO or COO, B 'is a bond or NH, NCH3, NR *, (CH2) n (n is 0, 1 or 2) , O, S, S02, CO or COO, R * being an alkyl1, aryl1 or heteroaryl1; W is a bond or a linker selected from NH, NHCO, NHCOO, NHCONH, NHS02, NHS02NH, CO, CONH, COO, COCH2, (CH2) n (n is 0, 1 or 2), CH2-CO, CH2COO, CH2 -NH, O, OCH2, S, S02, and S02NH; R1 is: a) a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a basic nitrogen pendant; b) an aryl or heteroaryl group optionally substituted by an alkyl or aryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; c) an alkyl1, aryl1 or heteroaryl1. 2. The compound according to claim 1, further characterized in that R6 is (v), R4 is H or CH3, A-B-B 'is CO-NH. 3. The compound according to claim 1, further characterized in that it is of formula II:

FORMULA II wherein X is R or NRR ', and wherein R and R' independently are chosen from H, an aryl, a heteroaryl, an alkyl, or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally bearing a pendant basic nitrogen functionality; or an aryl, a heteroaryl, an alkyl or a cycloalkyl group substituted with an aryl, a heteroaryl, an alkyl or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally bearing a pendant basic nitrogen functionality, R2 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R5 is hydrogen, halogen or a branched or alkyioalkyi group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy; (iii) a five-membered aromatic ring heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen , an alkyl group conferring from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, NO2 or SO2-R, wherein R is a linear or branched alkyl group that confers one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a Q < -lc i i, or ~ * ??, D Di-. and CR, . and ./irO. q Tu -e r μvu? - + t a Q Jc "basic nitrogen pendant.

4. The compound according to claim 1 or 3, further characterized in that R1 and X, respectively, are an alkyl, aryl or substituted heteroaryl group carrying a pendant basic nitrogen functionality represented for example by the aam structures shown below, wherein the wavy line and the arrow line correspond to the point of attachment to the core structure of formula I or II. to

5. The compound according to claim 4, further characterized in that the arrow is a point of attachment to the structure via a fenium group.

6. The compound according to claim 1 or 3, further characterized in that R6 is a 3-pyridyl group (see later structure g), or a 4-pyridyl group (see structure h below), the wavy line in the structure g and h corresponds to the point of attachment to the core structure of formula I or II. g

7. - The compound according to claim 3, further characterized by having the formula 11-3: wherein Ra, Rb, Rc, Rd, Re are independently chosen from H or an organic group which may be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloaiqu or, a p ?? or optionally substituted heyeroap group with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; a -S02-R group wherein R is an alkyl, aryl cycloalkyl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a group -CO-R or -CO-NRR ', wherein R and R' independently are chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group, optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; Ra, Rb, Rc, Rd, Re can also be - a halogen such as I, Cl, Br and F; - a group NRR 'wherein R and R' are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - an OR group where R is H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted by at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; a -S02-R 'group wherein R' is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a group NRaCORb where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a group NRaCONRbRc where Ra and Rb are H or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroavironment and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or carrying a pendant basic nitrogen functionality; - a COOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a CONRaRb, where Ra and Rb are a hydrogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a nitrogen functionality basic pendant; a cycloalkyl, an aryl or a heteroaryl group optionally substituted with at least one heteroaryme, notably a halogen selected from i, Ci, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an NHCOOR, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - an OS02R, where R is a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or a heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or a heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a NRaOS02Rb where Ra and Rb are a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and / or carrying a pendant basic nitrogen functionality; Ra can also be a hydrogen; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a nitrogen functionality basic pendant; - a CN group; - a trifluoromethyl group; R 4 is hydrogen, halogen or a linear or branched alkyl group containing 1 to 10 carbon atoms, trifluoromethyl or alkoxy; R6 is one of the following: (i) an aryl group such as phenyl or a substituted variant thereof carrying any combination, at any position on the ring, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (ii) a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally carry any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, tpilororpetpetiQ and cox; An ionic-cyclic aromatic five-membered ring group such as, for example, 2-thienyl, 3-fienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally carry any combination of one or more substituents such as halogen, an alkyl group conferring from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy; (iv) H, a halogen selected from I, F, Cl or Br; NH2, N02 or S02-R, wherein R is a linear or branched alkyl group containing one or more groups such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and / or carrying a pendant basic nitrogen functionality.

8. The compound according to claim 7, further characterized in that it is selected from: N- (2-fluoro-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-4-yl) -thiazol-2-ylamino) -benzamide; N- (3-fluoro-phenyl) -4-mephi [-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, 4-methyl-3- (4- pyridin-4-yl-thiazol-2-ylamino) -N- (3-trifluoromethyl-phenyl) -benzamide, 4-methyl-N- (4-methyl-3-trifluoromethyl-phenyl) -3- (4-pyridin- 4-yl-thiazol-2-ylammon) -benzamide, N- (2-fluoro-5-trifluoromethyl-phenyl) -4-mephyl-3- (4-pyridin-4-yl-thiazole-2- ilamino) -benzamide, N- (4-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (4-fluoro- phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3-fluoro-4-methyl-phenyl) -4-methyl-3 - (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (4-tert-butyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazole- 2-amino) -benzamide, N- (3-cyano-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3-cyano) -4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3-bromo-phenyl) -4-methyl- 3- (4- A, x;) or IA -t-? I? E? Ii-o- (< + -pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3, 5-dibromo-4-methyl-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) - benzamide, N- (3-chloro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3-chloro-4-methyl-phenyl) - 4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (3-methoxy-phenyl) -4-methyl-3- (4-pyridin-4-yl); lthiazol-2-ylamino) -benzamide, 4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -Nm-tolyl-benzamide, N- (4-fluoro-3-methyl-phenyl) -4-metii-3- (4-pyridin-4-ii-thiazoi-2-ylamino) -benzamide, N- (3-iodo-4-methyl-phenyl) -4-methyl-3- (4- pyridin-4-yl-thiazol-2-ylamino) -benzamide, 4-methyl-N- (3-nitro-phenyl) -3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, 4 -methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -N-p-tolyl-benzamide, 4-methyl-N-phenyl-3- (4-pyridin-4-yl-thiazole- 2-ylamino) -benzamide, N- (3,4-dimethyl-phenol) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylammon) -benzamide , 4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -N- (3-trifluoromethoxy-phenyl) -benzamide, N- (3,4-dicyano-phenyl) ) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (2-fiuoro-5-methyl-phenyl) -4-methyl-3- (4 -pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (2,4-difluoro-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylammon) -benzamide, N- (4-cyano-2-fluoro- phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (2-fluoro-4-methyl-phenyl) -4-methyl-3- (4- pyridin-4-yl-thiazol-2-ylamino) -benzamide, N- (2,4-d-fluoro-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazole-2) -lamino) -benzamide, N- (4-cyano-2-fluoro-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, N- (2- fluoro-4-methyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, N- (4-cyano-phen L) -4-methyl-3- (4-pyridn-3-yl-thiazol-2-ylamino) -benzamide, N- (4-phenyl-phenyl) -4-methyl -3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, 4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -Nm-tolyl-benzamide, 4-rr? Eiiii-3- (4-? Iridin-3-yl-dia -2-amino) -N- (3-trifluoromethyl-phenyl) -benzamide, 4-methyl-N- (4-methyl-3-trifluoromethyl-phenyl) -3- (4-pyridin-3-) il-thiazol-2-ylamino) -benzamide, N- (2-fluoro-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide , N- (4-cyano-3-trifluoromethyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, N- (4-cyano) -3-methyl-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, 4-methylN- [4- (4-methyl-p-piperaz) n-1-ylmethyl) -3-trifluoromethyl-phenyl] -3- (4-pyridin-4-yl-thiazol-2-ylamino) -benzamide, 4-methyl-N-. { 4- [1- (4-methyI-piperazin-1-yl) -ethyl] -phenyl} -3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide, N- (3-dimethylamino-phenyl) -4-methyl-3- (4-pyridin-4-yl-thiazole- 2-ylamino) -benzamide, N- (3-dimethylamino-phenyl) -4-methyl-3- (4-pyridin-3-yl-thiazol-2-ylamino) -benzamide.

9. A pharmaceutical composition comprising a compound according to claim 1 to 8.

10. The pharmaceutical composition according to claim 9, further characterized in that it is suitable for oral administration.

11. A dermopharmaceutical or cosmetic composition for topical administration of a compound according to one of claims 1 to 8.

12. A veterinary composition comprising a compound according to one of claims 1 to 8. 13.- The Use of a compound as defined in one of claims 1 to 8 for the manufacture of a medicament for the treatment of a disease selected from immunocompromised diseases, allergic diseases, bone loss, cancers such as leukemia and GIST, tumor angiogenesis, diseases inflammatory, such as arthritis, inflammatory bowel diseases (IBD), interstitial cystitis, mastocytosis, infectious diseases, metabolic disorders, fibrosis, diabetes and CNS disorders.