MX2008008705A

MX2008008705A - 2-carbamide-4-phenylthiazole derivatives, preparation thereof and therapeutic use thereof

Info

Publication number: MX2008008705A
Application number: MXMX/A/2008/008705A
Authority: MX
Inventors: Casellas Pierre; Jegham Samir; Floutard Daniel; Fraisse Pierre; Hourcade Stephane
Original assignee: Sanofi Aventis Societe Anonyme
Priority date: 2006-01-06
Filing date: 2008-07-03
Publication date: 2008-09-26

Abstract

The invention relates to 2-carbamide-4-phenylthiazole derivatives having the following general formula (I). The invention also relates to pharmaceutical compositions containing a compound of general formula (I).

Description

DERIVATIVES OF 2-CARBAMIDE-4-PHENYLTIAZOL. YOUR PREPARATION AND YOUR APPLICATION IN THERAPEUTICS The invention relates to 2-carbamide-4-phenylthiazole derivatives, to their preparation and to their application in therapy. The subject of the invention is the compounds that respond to the following formula (I): wherein: Ri represents a hydrogen atom, a halogen atom, an alkyl group (C? -8), trifluoroalkyl (C? -C), -OH, -O-alkyl (C? -8), -O-trifluoroalkyl (C? -C8), -O-alkyl (d-C? J-cycloalkyl (C3-C? 0), -O-cycloalkyl (C3-C10), -O-CH2-CH = CH2, -S-alkyl (C1 -C4); R2 represents a hydrogen atom, a halogen atom, a group -OH, alkyl (C? -C8), trifluoroalkyl (C1-C4), perfluoroalkyl (C1-C4), cycloalkyl (C3-C10), -O-alkyl (C? -8), -O-alkyl (C? -C8) -cycloalkyl (C3-C10), -O-cycloalkyl (C3-C10), -O-CH2-CH = CH2) -alkyl (C? -8) -cycloalkyl (C3-C8); Y represents a hydrogen atom or a halogen; p represents 2 or 3; - R3 represents: a1) a group of formula - (CH2) a-A in which a represents 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R7 is selected from the group consisting of • alkyl (C? -C8) -COO-alkyl (C? -8), • -CO-alkyl (C? -8) wherein alkyl is substituted by less a halogen atom, • -cycloalkyl (C3-C10), • phenyl, • -COO-cycloalkyl (C3-C10), • -SO2-alkyl (C? -8) in which the alkyl is substituted by at least a halogen atom, • -SO2-phenyl in which the phenyl is substituted by at least one -O-alkyl group (C? -C8), • -SO2-heteroaryl wherein the heteroaryl is a pyrazole, an isoxazole or an imidazole and wherein the heteroaryl is independently substituted by at least one group selected from halogen or -alkyl (C? -C8),? -SO2-N ((C? -C?) alkyl) 2, • -SO2-OH , • -SO2-cycloalkyl (C3-C10), -CO-NH (alkyl (C? -Cβ)), alkyl (C? -Cβ) -CN, -alkyl (C? -8) -imidazole, -alkyl ( C? -C8) -COOH, -alkyl (C? -C8) -COO "M +, -alkyl (d-C8) -OH, -alkyl (C? -8) -tetrazole, -alkyl (C? -C8 ) -CO-NH2, -alkyl (d-C8) -CO-NH (alkyl (C? -C8)),? -alkyl (C? -C8) -CO-NH ((C3-C10) cycloalkyl, -alkyl (C? -8) -CO-N (alkyl (d-C8) )) ((C3-C10) cycloalkyl, -alkyl (d-C8) -CO-N ((C? -C8) alkyl) 2, -alkyl (C? -8) -CO-N (cycloalkyl (C3-) C10)) 2, wherein M + is an alkali metal cation selected from L +, Na + and K +, and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different; a2) a group of formula -CO (CH2) b-A wherein b represents 0, 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R7 is as defined above; a3) a group -B in which B is selected in the group constituted by wherein R7 is as defined above, a4) a group of formula - (CH2) a-C wherein a represents 1, 2, 3 or 4, and C is selected from the group consisting of wherein - R8 is selected from the group consisting of • a hydrogen atom, • an alkyl group (C? -8), • alkyl (C? -8) -COO-alkyl (C? -8), • -CO-alkyl (C? -C8) in which the alkyl is optionally substituted by at least one halogen atom, • -cycloalkyl (C3-C10), • phenyl, • -COO-cycloalkyl (C3-C10), • -SO 2 -alkyl (C? -8) in which the alkyl is optionally substituted by at least one halogen atom, • -SO 2 -phenyl in which the phenyl is optionally substituted by at least one -O-alkyl group ( C? -C8),? -SO2-heteroaryl wherein the heteroaryl is a pyrazole, an isoxazole or an imidazole and in which the heteroaryl is optionally independently substituted by at least one group selected from halogen or -alkyl (C -C8), -SO-N ((d-C8 alkyl)) 2-, SO2-OH, • -SO2-cycloalkyl (C3-C10) -, CO-NH (alkyl (d-C8)), -alkyl (C? -C8) -CN, -alkyl (C? -8) -midazole, -alkyl (C? -8) -COOH, • -alk (C? -C8) -COOM +, -alkyl (C? -C8) -OH, -alkyl (C? -C8) -tetrazole, -alkyl (C? -C8) -CO-N H2, -alkyl ( d-C8) -CO-NH ((d-C8) alkyl), • -alkyl (C? -8) -CO-NH ((C3-C10) cycloalkyl, -alkyl (C? -8) -CO- N ((d-C8) alkyl ((C3-C3) cycloalkyl), (C? -C8) alkyl-CO-N ((C-C8) alkyl) 2, -alkyl (C? -8) - CO-N ((C3-C? 0) cycloalkyl) 2, wherein M + is an alkali metal cation selected from Li +, Na + and K +, and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different; - R9 is selected from the group consisting of: hydroxyl, O-alkyl (C? -8), -O-trifluoroalkyl (C? -8), -O-alkyl (C? -8) -cycloalkyl (C3-C10), -O-cycloalkyl (C3-C10), - Ra, Rb, Rc and Rd are independently a hydrogen atom or a methyl group, with at least one of Ra, Rb, Rc and Rd being a methyl group; - Re, Rf, Rg and Rh are independently a hydrogen atom or a methyl group; a5) a group of formula -CO (CH2) -C wherein b represents 0, 1, 2, 3 or 4, and C is selected from the group consisting of: wherein: - R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are as defined above, a6) a group -D where D is selected from the group consisting of: wherein: - R8, R9) Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are as defined above, in the form of base or addition salt to an acid, as well as in the form of hydrates or of solvates. A preferred halogen is fluorine. The compounds of the formula (I) may have one or more asymmetric carbon atoms. They can exist, therefore, in the form of enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures, including racemic mixtures, form part of the invention. The compounds of formula (I) may exist in the form of bases or acid addition salts. Such addition salts form part of the invention. These salts are advantageously prepared with pharmaceutically acceptable acids, but the salts of other acids useful, for example, for the purification or isolation of the compounds of the formula (I) also form part of the invention. The compounds of formula (I) can also exist in the form of hydrates or solvates, that is, in the form of associations or combinations with one or more water molecules or with a solvent. Such hydrates and solvates also form part of the invention. In the context of the present invention, it is meant by: - Ct-Z in which tyz can have the values of 1 to 10, a carbon chain which may have, for example, carbon atoms, for example, C1.3, a carbon chain which it can have from 1 to 3 carbon atoms; - a halogen atom is, for example, a fluorine, chlorine, bromine or iodine atom; - an alkyl group: a linear or branched saturated aliphatic group, optionally substituted with a halogen atom. By way of examples, the methyl, ethyl, propyl, isopropyl, butyl, isobutyl groups may be mentioned. tertiary butyl, pentyl, 2-fluoroethyl, etc.; - a cycloalkyl group: a cyclic alkyl group. By way of example, mention may be made of the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl groups, etc .; - a perfluoroalkyl group: an alkyla radical, as defined above, in which all carbon atoms are substituted with fluorine atoms. Among the subject compounds of the invention, mention may be made in particular of the following compounds of formula (I a): (1a) in which Ri, R2, R3 and Y are as defined above. The preferred compounds of the invention of formula (1a) are those in which Ri is in position 2 and R2 is in position 5 of the phenyl. The compounds of the invention of formula (1a) are those in which Ri is in position 2 and R2 is in position 5 of the phenyl. Among the compounds object of the invention, mention may be made of the compounds for which: - R represents an -O-alkyl group (C? -C8) and / or; R2 represents an alkyl group (d-C8), cycloalkyl (C3-C10), perfluoroalkyl (C1-C4) or -O-alkyl (C? -8). Among these compounds, there may be mentioned a subgroup of compounds for which: - R1 represents an -O-alkyl group (C? -C8) and / or; R2 represents an alkyl group (d-C8), cycloalkyl (C3-C10) or -O-alkyl (d-C8). Among the compounds object of the invention, there may be mentioned a first group of compounds of general formula (I) to (a) in which R3 represents a group of formula - (CH2) aA in which a represents 1, 2, 3 or 4, and A is selected from the group consisting of: where R7 | R1 t R2, Y and p are as defined above. Among the compounds object of the invention, there may be mentioned a second group of compounds of general formula (I) or (1 a) in which R 3 represents a group of formula -CO (CH 2) bA wherein b represents 0, 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R7 R1 (R2, Y and p are as defined above.) Among the compounds object of the invention mentioned above in the first group and in the second group, there may be mentioned a subgroup of compounds for which A is select from the group consisting of: wherein R1 t R2, Y and p are as defined above. Among the compounds object of the invention, there may be mentioned a third group of compounds of general formula (I) or (l.a) in which R3 represents a group -B in which B is selected from the group consisting of: wherein R7, R,, R2, Y and p are as defined above. Among the compounds object of the invention mentioned so far, there may be mentioned a first subgroup of compounds for which R7 is selected from the group consisting of • -alkyl (C? -8) -COO-alkyl (C? -8), • -CO-alkyl (C? -C8) in which the alkyl is substituted by at least one halogen atom, • -cycloalkyl (C3-C10), • phenyl, • -SO2-alkyl (C? -8) in wherein the alkyl is substituted by at least one halogen atom, • -SO2-phenyl in which the phenyl is substituted by at least one -O-alkyl (C? -8), • -heteroaryl-SO2 group in which the heteroaryl is a pyrazole or an isoxazole or an imidazole and wherein the heteroaryl is independently substituted by at least one group selected from halogen or -alkyl (C? -C8), -SO2-N (alkyl (d-C? J, -SO2-OH, • -CO-NH ((C? -C8) alkyl-alkyl, (C? -C8) -CN, -alkyl (d-C8) -COOH, -alkyl (C? -8) - COO-M +, -alkyl (C? -C8) -OH,? -alkyl (C? -C8) -tetrazole, -alkyl (C? -8) -CO-NH n that M + is an alkali metal cation selected from Li +, Na * and K +, and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different. As well as a second subgroup of compounds for which R7 represents -SO2-cycloalkyl (C3-C10).

Among the compounds of formula (I) of the invention mentioned thus far, the following compounds can be mentioned, in particular: [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- ((S) -1-cid opropi l-pi peri di n-3-yl meth i) -pi perazin a-1 -carboxylic, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2- il] -amide of 4- (1-sopropi I ca rba m oi l-pi peri di n-3-i I) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2 4- (1-cyclopropanesulfonyl-piperidin-4-yl) -piperazine-1-carboxylic acid, 3-ethyl ester (3-methyl-3-yl) -amide; {. 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl] -piperidin-1-yl) -propionic acid, 3 - (( R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -pi perazin-1-ylmethyl]. -pi peri di n-1 -yl) -propane, ethyl ester of 4 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -pi perazin -1-ylmethyl.}. -piperidin-1 -yl) -butyric, acid 4 - ((R) -3-. { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -pi perazin-1-yl methyl} -pi peri di n-1-yl) -butyral, 5 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-ethyl ester -ylcarbamoyl] -piperazin-1-ylmethyl.}. -piperidin-1-yl) -pentanoic acid, 5 - ((R) -3-. {4- [4- (5-cyclohexyl-2-methoxy-phenyl)] ) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl.}. -piperidin-1-yl) -pentanoic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4-cyclohexyl-piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) - piperazi na-1-carboxylic, More particularly, the following compound may be mentioned: 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4) acid -yl) -piperazine-1-carboxylic acid, Among the compounds of formula (I) of the invention mentioned thus far, mention may be made principally of the following compounds: [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole- 2-yl] -amide of 4 - ((S) -1 -cyc opropy I -pi peri di n-3-i I m eti I) -piperazi na- 1 -carboxyl ico, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-carbonyl I) -piperazine-1-carboxylic acid, [4 - (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1 -carbamoylmethyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid, acid ( (S) -3-. { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl} -piperidin-1 -yl) -acetic[4- (5-cyclohexyl-2-methoxy-phenyl) -5-fluoro-thiazol-2-yl] -amide of 4 - ((S) -1-cyclopropyl-pi-peridin-3-yl] methyl] -piperazine-1-carboxylic acid, 4- (tetrahydro-pyran-4-ylmethyl) -piperazine-1-carboxylic acid ester, 1-4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide. Ethyl ((S) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl} -piperidin-1- il) -acetic, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(R) -1 - (2-cyano-ethyl) -piperidin-3 -amide] -ylmethyl] -piperazine-1-carboxylic acid, sodium salt of 3 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole -2-yl carbamoyl] -piperazin-1-ylmethyl.}. -piperidin-1-yl) -propionic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(R ) -1 - (2-carbamoyl-ethyl) -piperidin-3-ylmethyl] -piperazine-1-carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] 4 - ((R) -1-Cyclopropyl-piperidine-3-carbonyl) -piperazine-1-carboxylic acid, [4- (5-butyl-2-e 4- ((S) -1-ci cl opropi I-pi peri di n-3-i I meti I) -pi perazin a-1 -carboxylic acid, (4-methoxy-phenyl) -thiazol-2-yl] -amide; [4- (5-cyclopentyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1 -cyc-opropi I-pi peri di n-3-i I meti I ) -pi perazin a-1-carboxylic acid, 4- (5-butyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1 -cyc opropi I-pi peri di n-3-ii meti I) -piperazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- ( (S) -1-ci ani m eti I -pi peri di n-3-i I meti I) -piperazi na-1 -carboxylic, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2 -yl] -amide of 4 - ((R) -1-cyclic opropyl-pi-peri-di-3-i) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy) phenyl) -thiazol-2-yl] -amide of 4- (1-cyc-opropi I-pi peri di n-4-i) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2) 4 - ((S) -1-cyclopropanesulfonyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid-4-cyclohexane-4-cyclohexane-4-cyclohexane-4-cyclohexane] 4-Exo-2-methoxy-phenyl) -thiazol-2-yl] -amide of the acid 4 - ((S) -1-f eni-pi-peri-di-3-i I-meti I) -piperazi na- 1 - carboxylic acid 2-. { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl} -piperidin-1-sulfonic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(S) -1 - (2-hydroxy-ethyl) -pi] penten-3-ylmethyl] -piperazyl-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(S) -1 - (2, 2, 2-trifluoro-acetyl) -piperidin-3-ylmethyl] -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -5-fluoro-thiazol-2-yl ] 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl-amide acid) - ((S) -1-dimethylsulfamoyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] [(S) -1 - (2H-tetrazol-5-ylmethyl) -pi-peri-di-3-ylmethyl] -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) - thiazol-2-yl] -amide of 4- [1 - (5-chloro-1,3-di methyl-1 H-pi-razol-4-sulfonyl) -piperidin-2-ylmethyl] -piperazine-1-carboxylic acid 4- [1 - (1,3-di methyl-1 H- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] pyrazol-4-sulfonyl) -piperidin-2-ylmethyl] -piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- [1 -] (1, 5-di methyl-1 H-pi-razol-4-sulfonyl) -pi peri-di-2-i I meti I] -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy 4- [1 - (1-methyl-1 H-pi-razol-4-sulf onyl) -piperidin-2-ylmethyl] -piperazine-1-carboxylic acid-phenyl) -thiazol-2-yl] -amide. 4- [1 - (5-Methyl-isoxazole-4-sulfonyl) -piperidin-2-ylmethyl] 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] - piperazine-1-carboxylic acid, 4- [1 - (1-methyl-1 H-imidazole-4-sulfonyl) [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] -piperidin-2-ylmethyl] -piperazine-1-carboxylic acid, 4- (1-di methylsulfanyl-piperidin- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] 2-ylmethyl) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- [1 - (2, 2, 2-trifluoro-ethanesulfonyl) -piperidin-2-ylmethyl] -piperazine-1-carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] 4- [1 - (4-m-ethoxy-benzenesulfonyl) -pi peri-di-2-i-methyl] -piperazine-1-carboxylic acid, [4- (5-cyclopentyl-2-ethoxy-phenyl) - thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-yl] ] -amide of 4- [1 - (3,5-di-methyl-I-isoxazole-4-sulfonyl) -pi peri-di-2-i-methyl] -piperazine-1-carboxylic acid, [4- ( 4- (Butyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pi ran-4-i) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl- 2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(S) -1 - (1 -methyl-1 Hi my dazol-4-sulfonyl I) -piperidin-3-ylmethyl] - piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, [ 4- (5-cyclopentyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (t etrahydro-pyran-4-yl) -piperazine-1-carboxylic acid,. { 4- (5-Butyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, 4- (2-methoxy) 4- (Tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, 4- (5-propyl-2-methoxy-phenyl) -thiazole-5-propoxyphenyl) -thiazol-2-yl] -amide. 2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of the 4- (Tetrahydro-pyran-4-yl) - [1,4] diazepane-1-carboxylic acid Among the compounds of the invention, a fourth group of compounds of general formula (I) or (I) may be mentioned. a) in which R3 represents a group of formula - (CH2) aC in which a represents 1, 2, 3 or 4, and C is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R R2, Y and p are as defined above. Among the compounds object of the invention, there may be mentioned a group of compounds of general formula (I) or (1 a) in which R3 represents a group of formula -CO (CH2) bC wherein b represents 0 , 1, 2, 3 or 4, and C is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, R2, Y and p are as defined above. Among the compounds object of the invention mentioned above in the fourth group and in the fifth group, there may be mentioned a first subgroup of compounds for which C is selected from the group consisting of: wherein R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R,, R2, Y, and p are as defined above. Among the compounds object of the invention mentioned above in the fourth group and in the fifth group, a second subgroup of compounds can be mentioned for which C represents: wherein R8, Ra, Rb, Rc, Rd, Ri, R2, Y and p are as defined above. Among the compounds object of the invention, there may be mentioned a sixth group of compounds of general formula (I) or (l.a) in which R3 represents a group -D in which D is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, R2, Y and p are as defined above. Among this sixth group, there may be mentioned a subgroup of compounds for which R8 is a hydrogen atom or an alkyl (C? -C8) alkyl group. Among the compounds of formula (I) of the invention mentioned in the third, fourth and fifth groups and their subgroups, mention may be made, in particular, of the following compounds: [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2 -amide of 4- (1,1-di-oxo-hexahi-dro-1? 6-ti-opi-4-i-I) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy) phenyl) -thiazol-2-yl] -amide of 4- (4-hydroxy-cid-ohexyl) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole- 2-yl] -amide of 4- (1, 2, 2, 6, 6-pentamethyl-pi-pen-n-4-i) -piperazine-1 -carboxylic acid, 4- (5-cyclohexyl-2- 4- (2,2,6,6-tetramethyl-piperidin-4-yl) -piperazine-1-carboxylic acid methoxy-phenyl) -thiazol-2-yl] -amide, [4- (5-cyclohexyl-2 4- (2,2-di methyl-tetrahydro-pyran-4-i I meti I) -piperazine-1-carboxylic acid [4-methoxy-phenyl] -thiazol-2-yl] -amide. 4- (tetrahydro-thiopyran-4-yl) -piperazine-1-carboxylic acid 5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide, Certain compounds intermediates useful for the preparation of the compounds of formula (I) may also serve as the final product of formula (I), as will appear in the examples provided hereinafter. Similarly, certain compounds of formula (I) of the invention can serve as intermediate compounds useful for the preparation of compounds of formula (I) according to the invention. In the text that follows, the protective group Gp is understood to be a group that allows, on the one hand, to protect a reactive function such as a hydroxyl or an amine during a synthesis and, on the other hand, to regenerate the intact reactive function at the end of the synthesis. yes synthesis Examples of protecting groups as well as protection and deprotection methods are provided in "Protective Groups in Organic Synthesis", Green et al. , 2nd Edition (John Wiley &Sons, Inc., New York). Outgoing group X is understood, in the text that follows, to be a group that can be easily separated from a molecule by breaking a heterolytic bond, with the output of an electronic pair. This group can thus easily be replaced by another group in the case of a substitution reaction, for example. Said leaving groups are, for example, halogens or an activated hydroxyl group such as a mesyl (methanesulfonyl), tosyl (toluenesulfonyl), triflate, acetate, etc. Examples of leaving groups as well as references for their preparation are provided in "Advances in Organic Chemistry", J. M arch, 3rd Edition, Wiley I nterscience, p. 310-316. In the following text, the precursor of Ri, R2 or R3 is understood to be a substituent R'i, R'2 or R'3 which can be converted into R (R2 and R3 by one or more chemical reactions. Z in the following text, a leaving group or a functional derivative of carboxylic acid, such as an acid chloride, a mixed or metric anhydride, or else the acid activated in a timely manner for example with benzotriazole-1-yloxytri-hexafluorophosphate ( dimethylamino) phosphonium (BOP), O-benzotriazole-1-yl-N, N, N ', N'-tetramethyl uronium hexafluorophosphate (HBTU) or O-benzotriazol-1-yl-N, N, N' tetrafluoroborate, N'-tetramethyl uronium (TBTU) When one or several substituents R, R'2 and / or R'3 represent a group containing an amine or hydroxyl function, these functions may be protected intermediately: an amine function may be protected by an alkanoyl, benzyl, tert-butoxycarbonyl (Boc), benzyloxycarbonyl, or 9-fluorenylmethoxycarbonyl group (Fmoc), for example; a hydroxyl function may be protected in the form of ether or ester, for example. The compounds of the invention can be prepared according to different methods described in the present patent application. According to another aspect, the present invention relates to the methods of preparing the products of formula (I) and their intermediates. The compounds of formula (I) of the invention can be prepared according to the following general scheme 1.

Scheme 1 OH) According to scheme 1, the compounds of the invention are obtained by coupling the aminothiazole derivative of formula (II) in which Ri, R2, Y are as defined in the previous text, with an amino derivative of formula (III) ) in which R'3 represents a precursor group of R3 or a group R3 as defined in the previous text and p is as defined in the previous text. The aminothiazole derivatives of formula (II) can be obtained according to the methods described in patent application WO 2004/096798. According to scheme 1, the aminothiazole derivative of formula (II) is placed in the presence of a coupling agent for 2 to 16 hours, and then with the amine derivative of formula (III) for 0.5 to 4 hours. The coupling agent may be chosen from those known to one skilled in the art, for example, phosgene, di- (N-succinimidyl) carbonate or 1,1 '-carbonyl-diimidazole, according to the methods described in "Encyclopedia of Reagents for Organic" Synthesis », LA Paquette, volume 2, p. 1006; volume 4, p. 2304; volume 6, p. 4107.

The reaction can be carried out in different solvents, for example, dichloromethane, dimethylformamide or toluene, in the presence of a base such as triethylamine or K2CO, at a temperature ranging from 0 ° C to 100 ° C. The amino derivatives of formula (III) are known or can be prepared according to the methods described mainly in WO 87/01706 or according to the methods described in the following text. In the text that follows, groups A 'and C represent respectively a precursor group of group A or C, or a group A or C such as defined above. The compounds of formula (III) in which R'3 represents a precursor group of R3 or a group R3 as defined in the preceding text and in which p is as defined in the preceding text, are obtained from compounds of formula (IV) by deprotection of the nitrogen of the piperazine or protected homopiperazine according to methods known to those skilled in the art or described in the literature (WO 03/1 04230 and WO 03/057145). As an example, you can proceed as follows: e '-v - - («O-)' 'N' '*' • -,: VÍ; The compounds of formula (IV) are commercial or can be synthesized from commercial compounds, according to methods known to the person skilled in the art. The compounds of formula (IV), wherein R'3 represents a precursor group of the group R3, wherein R3 represents a group -CO (CH2) bA or -CO (CH2) bC (compounds of formula (IV.2) or ( IV.5)), can also be obtained according to scheme 2 below: Scheme 2 ) ) According to scheme 2, a piperazine or a monoprotected homopiperazine (Gp = BOC or Gp = benzyl) reacts with a compound of formula (V.1) or (V.2) in which Z represents a leaving group, or a resulting group of activation of a carboxylic acid function, respectively to give the compound of formula (IV.2) or (IV.5) by acylation or coupling of peptide type in the presence of a base such as K2CO3, triethylamine, diisopropylethylamine or cesium carbonate optionally in the presence of a coupling reagent such as BOP, TBTU or CDI, in a solvent such as THF, acetonitrile or DMF at temperatures ranging from 0 ° C to 150 ° C.

The compounds of formula (IV), in which R'3 represents a precursor group of the group R3, R3 representing a group -CO (CH2) aA or - (CH2) aC (compounds of formula (IV.1) or (IV .4)), can also be obtained according to the following scheme 3: Scheme 3 - (CH2) ß-A ') = - (CH2) 8-C) According to this process, a piperazine or a monoprotected homopiperazine (Gp = BOC or Gp = benzyl) react with an aldehyde of formula (VI. 1) or (VI.2) to give respectively the compound of formula (IV.1) or (IV.4) under the conditions of a reductive amination reaction in the presence of a reducing agent such as NaHB (OAc) 3, NaBH3CN in a solvent such as 1,2-dichloroethane, dichloromethane, methanol, THF at temperatures varying from 0 ° C to 70 ° C (Synth Commun., 1998, 28 (10), 1897-1905, J. Org. Chem., 1992, 57 (11), 3218-3225, J. Org. Chem, 1996, 6 L 3849-3862, Tetrahedron Lett., 1990, 31_, 5595-5598). Alternatively, the compounds of formulas (IV.1) and (IV.4) can be synthesized by a substitution reaction according to the procedure illustrated in scheme 4 below: Scheme 4 G CH2) ß-A ') - (CH2) a-C) According to scheme 4, a piperazine or a mono-protected homopiperazine (Gp = BOC or Gp = benzyl) reacts with a compound of formula (Vil.1) or (Vil.2) wherein X represents a leaving group to give respectively the compound of formula (IV. I) or (IV.4). The reaction is carried out without solvent or in a solvent such as tetrahydrofuran, dimethylformamide, toluene, or acetonitrile in the absence of base or in the presence of a base such as triethylamine or K2CO3, at temperatures ranging from room temperature to 200 ° C, for 1 to 24 hours. The compounds of formula (IV), in which R'3 represents a precursor group of the group R3, wherein R3 represents a group -B or -D (compounds of formula (IV.3) or (IV.6)), can be prepared by reaction of a piperazine or of a mono-protected homopiperazine (Gp = BOC or Gp = benzyl) and of a ketone B 'precursor of B or of a D precursor ketone D', by reductive amination reaction in the presence of a reducing agent such as NaHB (OAc) 3, NaH 3 CN in a solvent such as 1,2-dichloroethane, methanol, dichloromethane, THF at temperatures ranging from 0 ° C to 70 ° C according to the following scheme: Scheme 5 The B 'and D' ketones used are commercially available or can be synthesized according to the methods described in Organic Process Research & Development, 2004. 8, 939; Synthesis, 1989, 10, 767 The compounds of formula (I) can also be prepared according to the following scheme 6. Scheme 6 0X > or • * < PHA (va.1) «or» c According to scheme 6, the aminothiazole derivative of formula (II) as defined in the previous text is coupled to a piperazine or a monoprotected homopiperazine (Gp = BOC or Gp = benzyl) to give the compound of formula (VI I I). The reaction is carried out under the same conditions as those described above for Scheme 1. The compound of formula (VIII) is then deprotected to give a compound of formula (IX), according to methods known to one skilled in the art, which is reacted with a compound of formula (V.1), ( V.2), (VI .1), (VI .2), (VII. 1) or (Vil.2), or with a ketone of formula B 'or of formula D' such as defined above. This reaction is carried out according to the procedures described above for the synthesis of intermediates of formula (IV). In the general synthesis schemes, the starting compounds and the reagents, when their mode of preparation is not described, are commercially available or described in the literature, or they can be prepared according to the methods described therein, or they are known to the person skilled in the art. The following examples describe the preparation of compounds according to the invention. The numbers of the compounds of the examples correspond to those provided in Table I, which illustrates the chemical structures of some compounds according to the invention. In the preparations and examples that follow: - CyHex = a cyclohexyl group; - DSC = di- (N-succinimidyl) carbonate - CDl = 1, 1'-carbonyl-diimidazole - DCE = dichloroethane - TBM E = methyl tert-butyl ether - TA = room temperature, - DCM = dichloromethane, - DI PEA = diisopropylethylamine, - THF = tetrahydrofuran, BOP = benzotriazole-1-yl-oxy-tri s hexafluorophosphate (di methylamino) -f osph onium, - DM F = dimethylformamide, - Boc = tert-butyloxycarbonyl, - TFA = trifluoroacetic acid - TBTU = 2- (1 H-benzotriazole-1M) -1, 1, 3,3-tetramethyluronium tetrafluoroborate, - HOBT = hydroxybenzotriazole, - BSA = bis (trimethylsilyl) acetamide, - AcOEt = ethyl acetate , - AcCl = acetyl chloride. - PF = melting point (in degrees Celsius) as measured with a Büchi B545 device with a temperature gradient of 1 ° C per minute. - M H + = molecular mass of the shape of the molecule ionized by a proton. The compounds were analyzed by HPLC-UV-MS coupling (liquid chromatography - UV detection - mass spectrometry). The apparatus used, marketed by Agilent, is composed of an HP1 100 chromatograph equipped with an Agilent diode bar detector and a Quad MSD quad mass spectrometer. The analytical conditions are the following: Column: Symmetry C18 (50 x 2, 1 mm; 3.5 μm) Eluent A: H2O + 0.005% TFA at pH 3.15 Eluent B: CH3CN + TFA 0.005% Gradient: Times (min)% B 0 0 10 90 15 90 16 0 20 0 Column temperature: 30 ° C Flow rate: 0.4 ml / min. Detection:? = 220 nm The compounds for which "method B" is indicated in Table I are analyzed by LCMS under the following conditions: YMC Jsphere column (33 x 2, 1 mm, 4 μm, eluent: CH3CN + TFA al 0.05%: H2O + 0.05% TFA, gradient: 5:95 (0 min), after 95: 5 (2.5 min), then 95: 5 (3 min), flow rate: 1.3 ml / min, temperature: 30 ° C. - tr = retention time.

- RM N = nuclear magnetic resonance performed with a Bruker Avance 200 spectrometer (200 MHz). The solvent used is DM SO with deuterium and chemical shifts are expressed in relation to TM S. The abbreviations used are: - s = if nglete, - d = doublet, - d. d = unfolded doublet, - t = triplet, - m = multiplet, - sa = elongated singlet. - The analysis of the optical purity is measured by HPLC in Chiralpak AD (250 mm x 4.6) col umna eluted by a mixture of 80/20 CO2 / MeOH at 30 ° C with a flow rate of 3 'ml / min to P = 20 M Pa. The compounds are detected at 220 nm. - aD = rotating power. The rotary powers have been determined with a Perkin-Elmer 241 -MC polarimeter for the D-ray of sodium (? = 589 nm), the concentrations are expressed in 10 mg / ml, the measurements are carried out at room temperature. Example 1: 4 - ((S) -1-cyclopropyl-piperidin-3-ylmethyl-piperazine-1-carboxylic acid 4-cyclohexyl-2-methoxy-phenyl-thiazol-2-yl-amide (Compound No. 1) 1 .1 Preparation of tert-butyl ester of (Rl-3- ((methylsulfonyloxy) methyl) -piperidine-1-carboxylic acid To a solution of 5 g of tert-butyl ester of (R) acid -3- hydroxymethyl-piperidine-1-carboxylic acid in 80 mL of DCM cooled to 0 ° C, add 2.16 mL of methanesulfonyl chloride and then 3.86 mL of triethylamine.The medium is stirred 1 h 30 at 0 ° C and 0.7 mL of triethylamine and 0.54 mL of methanesulfonyl chloride are added.After 30 min at 0 ° C, the medium is hydrolysed, the organic phase is washed twice with water, then with a saturated solution of water. NaCl and dried over MgSO The medium is evaporated to give 6.8 g of a light yellow oil 1.2 Preparation of the (S) -3 - ((4-benzyl pi perazi n-1 - tert -butyl ester) i) methy-pi peri di na- 1 -carboxylic The brut product or obtained in stage 1 .1 is put into solution in 75 mL of toluene. 12.16 g of benzylpiperazine are added, the reaction medium is capped and heated for 5 hours at 150 ° C. After returning to RT, the medium is diluted in an ether / pentane mixture (1/1). Wash twice with a solution of NaHCO3, saturated, twice with water and with a saturated solution of NaCl. After drying over MgSO 4 and evaporating, the crude product is purified by flash chromatography on silica gel to provide 5.73 g of the expected solid. M H + = 374.3 at t = 5.26 min 1.3. Preparation of (S) -3- (piperazin-1-methylmethyl) piperidine-1-carboxylic acid tert-butyl ester A solution of 4.0 g of the compound obtained in step 1. 2 in 30 mL of methanol is hydrogenated in a closed reactor, under microwave irradiation, at 80 ° C for 10 min in the presence of 1.7 g of Pd / C with 10% humidity and 2.02 g of water format. ammonium. The medium is filtered and evaporated to provide 2.89 g of a colorless oil. 1 .4 Preparation of tert-butyl ester of (S) -3 - ((4- (4- (5-cyclohexy-l-2-methoxy-enyl) -thiazole-2-ylcarbamyl) -pe-perazin-1-I ) meti I) pi peri-di-na-1-carboxylic acid To a solution of 2.78 g of 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-amine, compound described in patent application WO 2004/096798 , in 7 mL of dichloromethane, 2.59 g of DSC are added and the medium is stirred for 12 hours at RT. 2.59 g of the compound described in step 1.3 are added and the medium is stirred for 3 hours at RT. The medium is hydrolyzed with a saturated NaHCO3 solution and extracted with DCM. The organic phase is washed with water, then with a saturated solution of NaCl. After drying over MgSO 4, the solution is concentrated and purified by flash chromatography on silica gel to give 4.0 g of the expected compound as a white solid. M H + = 598.7 at = 8.26 min 1.5 Preparation of f4- 5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-ill-amide of 4 - ((R) -1-piperidin-3 -ylmethyl) -piperazine-1-carboxylic acid To a solution of 4 g of the compound obtained in step 1. 4 in 10 mL of dioxane, add 42 mL of a 4 M solution of HCl in dioxane. The medium is stirred 4 h at RT. The medium is filtered, the solid is rinsed with ether then collected in OCM and treated with 1 M sodium hydroxide. The organic phase is washed with water, then with a saturated NaCl solution. After drying over MgSO 4, the solution is concentrated to give 3.16 g of the desired compound. M H + = 498.7 at = 6.27 ml n 1.6. Preparation of the 4- (cyclohexyl-2-methoxy-phenyl) -thiazole-2-yl-amide of 4 - ((S) -1 -cyclopropyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid To a solution of 0.2 g of the compound described in step 1.5 in 5 mL of M eOH, 0.35 g of (1-ethoxycyclopropoxy) is added. trimethylsilane then 0.05 g of NaBH 3 CN and 0.24 g of acetic acid. The medium is stirred for 2 h at 60 ° C. The medium is concentrated and collected in AcOEt. The organic phase is washed twice with a saturated NaHCO3 solution and with a saturated NaCl solution. After drying over MgSO, the organic phase is concentrated and purified by flash chromatography to provide 0.16 g of the expected product. PF = 88 ° C aD = + 4 ° (c = 1, MeOH) Example 2: 4- (1-isopropylcarbamoyl-piperidin-4-cyclohexyl-2-methoxy-phenyl-thiazole-2-ill-amide 3-yl-1-piperazine-1-carboxylic acid (Compound 2) 2.1 Preparation of 4- (1-benzylpiperazin-3-yl) piperazine-1-carboxylic acid tert-butyl ester To a suspension of 9.96 g of 1-benzylpiperidin-3-one monohydrochloride hydrate in suspension in 200 mL of DCM, add 20 mL of a 10% sodium hydroxide solution, stir the medium, decant the organic phase and wash with a saturated solution of NaCl After drying over MgSO 4, the organic phase is concentrated, the gum obtained is taken up in 180 mL of DCE, 10,1 g of Boc-piperazine and 15,9 g of NaBH (OAc) 3 are added and the medium is added. stir 12 h at RT The medium is concentrated and taken up in AcOEt The organic phase is washed twice with a saturated NaHCO3 solution and with a saturated NaCl solution After drying over MgSO4, the organic phase is concentrated to a 18.63 g of the expected product. PF = 103 ° C » 2. 2. Preparation of 1- (1-benzylpiperidin-3-yl) piperazine To a solution of 9.2 g of the compound obtained in step 2.1 in 85 mL of DCM, 30 g of TFA are added. The medium is stirred at RT for 5 h and concentrated. The obtained crude product is taken up in DCM and washed 4 times with a 2M sodium hydroxide solution. The organic phase is washed with a saturated solution of NaCl. After drying over MgSO 4, the organic phase is concentrated to provide 6.32 g of the expected product. RM N 1 H: d (ppm) = 7.28 (salt, 5H), 3.43 (salt, 2H). 2.88 (d, 1 H), 2.70 (d, 1 H), 2.64 (m, 4H), 2.43-2.22 (m, 5H), 1.85-1.58 ( m, 4H), 1, 39 (ddd, 1 H), 1, 15 (ddd, 1 H). 2.3 Preparation of 4- (1-benzyl-piperidin-3-yl) -piperazine-1-carboxylic acid 4- (cyclohexyl-2-methoxy-phenyl) -thiazole-2-in-amide The procedure is identical to that described in example 1 from the 4- (5-cyclohexyl-2-methoxyphenyl) -thiazole-2-amine described in the patent application WO 2004/096798 and the compound obtained in step 2.2. PF = 90 ° C 2.4 Preparation of 4-piperidin-3-yl-piperazine-1-carboxylic acid f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-yl-amide, A solution of 1.69 g of the compound obtained in step 2. 3 in 10 mL of DCE, 1.26 g of doroethyl chloroformate are added at 0 ° C. The medium is brought to RT and heated to reflux for 45 min. The medium is evaporated, taken up in 10 mL of MeOH and heated at reflux for 1 h. The crude product is filtered, the solid is washed with ether and dried to provide 1.27 g of the expected compound in the form of a trichlorohydrate. PF = 240 ° CM H + = 484.7 to 6.81 min 2.5 Preparation of f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-ip-amide of 4- (1-isopropylcarbamoyl-piperidin) -3-yl) -piperazin-1 -carboxylic acid To a solution of 0.2 g of the compound obtained in step 2. 4 in 1, 2 mL of DCM are added at 0 ° C, 0.06 mL of isopropyl isocyanate. The medium is stirred 2 h at 0 ° C then it is hydrolyzed with 5 mL of water and diluted with 10 mL of DCM. The organic phase is washed twice with a saturated NaHCO3 solution and with a saturated solution of NaCl. After drying over M gSO4The organic phase is concentrated and purified by flash chromatography to provide 0.16 g of the expected product. PF = 134 ° CM H + = 568-7 at = 7.61 min Example 3: f4- (S-cyclohexyl-2-methoxy-phenyl) -thiazole-2-in-amide of 4- (1-cyclopropanesulfonyl-piperidin-4) -yl) -piperazine-1-carboxylic acid (Compound No. 3) 3.1 Preparation of the 4- (1-benzyl-piperidine) 4- (cyclohexyl-2-methoxy-phenyl) -thiazole-2-ip-amide -4-ip-piperazine-1-carboxylic acid, The procedure is identical to that described in Example 1 starting from the 4- (5-cyclohexyl-2-methoxyphenyl) -thiazole-2-amine described in the patent application WO 2004 / 096798 and 1 - (1-benzyl-piperidin-4-yl) -piperazine PF = 81 ° C 3.2 Preparation of f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole- 2-in-amide of 4-piperidin-4-yl-piperazine-1-carboxylic acid To a solution of 1.77 g of the compound obtained in step 3. 1 in 10 mL of DCE, 1.31 g of chloroethyl chloroformate are added at 0 ° C. The medium is brought to RT and heated to reflux for 45 min. The medium is evaporated, taken up in 10 mL of MeOH and heated at reflux for 1 h. The crude product is filtered, the solid is washed with ether and dried to provide 1.27 g of the expected compound in the form of a trichlorohydrate. M H + = 484.6 to 6.21 min 3.3 Preparation of f4- (5-cyclohexyl-2-methoxy-phenyl-thiazole-2-ip-amide of 4-p-cyclopropanesulfonyl-piperidin-4-yl) - piperazine-1-carboxylic acid, To a solution of 0.2 g of the compound described in Preparation 3.2 in DMC, add 0.04 mL of cyclopropylsulfonyl chloride then 0.06 mL of triethylamine. The medium is stirred at RT for 4 h. The medium is diluted in DCM then hydrolyzed with 5 mL of water. The organic phase is washed twice with a saturated NaHCO3 solution and with a saturated solution. of NaCl. After drying over MgSO 4, the organic phase is concentrated and purified by flash chromatography to provide 0.18 g of the expected product. PF = 138 ° CM H + = 588.8 at = 7.49 min Example 4: Ethyl ester of 3 - ((R) -3- -f4- (5-cyclohexyl-2-methoxy-11-t-azole -2-carbamoyl-pi-perazin-1-yl-methypiperidin-1-yl) -propionic acid (Compound No. 4) To a solution of 0.2 g of the compound described in step 1. 5 in 2 mL of toluene, add 0.08 mL of triethylamine, then 0.05 mL of the ethyl ester of 3-bromo-propionic acid. The medium is stirred 48 h at RT. The medium is diluted in ethyl ether, then filtered. The filtrate is washed with water, then with a saturated solution of NaCl. After drying over MgSO 4, the organic phase is concentrated to provide 0.21 g of the expected product. MH + = 598.8 at = 6.84 min Example 5: Acid 3 - ((Rl-3- -r4- (5-cyclohexyl-2-methoxy-phenin-t-azo-2-lcarbamoyl-piperazine-1 -ylmetip-piperidin-1-yl) -propionic (Compound No. 5) To a solution of 0.208 g of the compound described in step 4 in 3 mL of methanol, 0.31 mL of sodium hydroxide are added at 0 ° C. The medium is stirred 24 h at RT The medium is concentrated, then it is collected in water, a solution of 6 N HCl is added dropwise until a precipitate appears, the solid is extracted in DCM, after drying over MgSO 4, the organic phase is concentrated to give 0.15 g of the expected product M H + = 570.7 at = 6.64 min PF = 144 ° C Example S: r4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole 4- (tetrahydro-pyran-4-yl) perazine-1-carboxylic acid (2-yl) -amide (Compound No. 11) This compound can be obtained according to the procedure described in preparation 1.4 between 4- (5- cyclohexyl-2-methoxyphenyl) thiazole-2-amine and 1- (tetrahydro-2H-pyran-4-yl) piperazine described in J. Med. Chem; EN: 47; 11; 2004; 2833-2838. Another method of synthesis is possible: 6.1 Preparation of 4- [4- (5-cyclohexyl-2-methoxy-phenyl-thiazol-2-ylcarbamoyl-piperazine-1-carboxylic acid tert -butyl ester To a solution of 3.0 g of 4- (5-cyclohexyl-2-methoxyphenyl) -thiazole-2-amine, compound described in the patent application WO 2004/096798, in 100 mL of dichloromethane, 2.9 g of DSC are added and the medium for 16 hours at RT 2.0 g of BOC-piperazine are added and the medium is stirred for 3 hours at RT The medium is hydrolyzed with a saturated NaHCO3 solution and extracted with DCM The organic phase is washed with water, then with a saturated solution of NaCl After drying over MgSO 4, the solution is concentrated and purified by flash chromatography on silica gel to give 5.1 g of the expected compound in the form of a beige solid M H + = 501 , 7 at = 1 1, 72 min 6.2 Preparation of f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-in-amide of piperazin-1-carboxylic acid To a solution of 5.1 g of the compound obtained in step 6.1 in 100 mL of dioxane, 19 mL of a 4 M solution of HCl in dioxane are added dropwise. The medium is stirred 4 h at RT. The medium is filtered, the solid is washed with ether and dried to give 4.38 g of a white powder. The solid is collected in DCM and treated with 1 M sodium hydroxide. The organic phase is washed with water, then with a saturated solution of NaCl. After drying over MgSO 4, the solution is concentrated to provide 3.7 g of the desired compound. MH + = 401, 6 at = 7, 19 min 6.3 Preparation of 4- (tetrahydro-pyran-4-yl) - f4- (5-cyclohexyl-2-methoxy-phenyl) -thiathyl-2-amide acid piperazine-1-carboxylic acid To a solution of 1.4 g of the piperazine obtained in step 6.2 in 13 mL of dichloroethane, add 0.4 g of dihydro-2H-pyran-4 (3H) -one, then 1, 59 g of NaBH (OAc) 3 and the medium is stirred 72 h at RT. The medium is concentrated and collected in DCM. The organic phase is washed twice with a saturated NaHCO3 solution and with a saturated solution of NaCl. After drying over MgSO 4, the organic phase is concentrated to provide 1.7 g of the expected product. The beige powder obtained is purified by flash chromatography on silica gel to give 1.42 g of the expected compound as a white solid. M H + = 484.7 at = 7.42 min PF = 226 ° C Example 7: r4- (5-cyclohexyl-2-methoxy-pheny1) -thiazole-2-ill-amide of 4- (tetrahydroform) -piran-4-carbonyl) -piperazine-1-carboxylic acid (Compound No. 13) To a solution of 41 mg of tetrahydro-2H-pyran-4-carboxylic acid in 0.7 mL of DCM, are added, at RT, 122 mg of TBTU, 26 mg of HOBt and 0.17 mL of DIPEA. The medium is stirred at RT for 1 hour and 15 minutes then 100 g of the compound described in step 6.2 are added. The medium is stirred for 12 hours at RT. The medium is taken up in DCM, washed three times with a saturated Na 2 CO 3 solution and then with a saturated NaCl solution. After drying over MgSO 4 and evaporation, 0.21 g of the crude reaction medium are recovered, which is purified by flash chromatography on silica gel to give 0.08 g of the expected compound as a white solid.

M H + = 51 3.7 at = 9, 88 min PF = 276 ° C Example 8: r4- (5-cyclohexyl-2-methoxy-phenyl-thiazole-2-ill-amide of 4- (tetrahydrofide) -piran-4-ylmethyl) -pi perazine-1-carboxylic acid (Compound No. 17) To a solution of 0.155 g of the piperazine obtained in step 6.2 in 1.5 mL of dichloroethane, 0.044 g of tetrahydro- 2H-pyran-4-carbaldehyde, after 1 hour of stirring at RT, 0.14 g of NaBH (OAc) 3 and the medium is stirred for 12 h at RT The medium is diluted in DCM The organic phase is washed twice times with a saturated solution of NaHCO3 and with a saturated NaCl solution After drying over MgSO4, the organic phase is concentrated to give 0.16 g of the crude product The solid is purified by flash chromatography on silica gel to give 0, 12 g of the expected compound in the form of a white solid MH + = 499.7 at = 7.75 min PF = 1 14 ° C Example 9: r4-5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-¡ 4 - ((S) -1-carbamoylmethyl-p-peridin-3-ylmethyl acid n-amide -piperazine-1-carboxylic acid (Compound No. 14) 9.1 Preparation of 3 - ((Sl-3-f4-f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoin-piperazine ethyl ester -1-ylmethyl) piperidin-1-iDacetic (Compound No. 18) This compound is synthesized from the compound described in preparation 1.5 and ethyl 2-bromoacetate according to a procedure identical to that described in preparation 4. 9.2 Preparation of the acid 3 - ((S) -3- (4-R4- (5-cyclohexyl-2-methoxy-phenit) -thiazol-2-ylcarbamoyl-1-piperazin-1-ylmethyl) piperidin-1-yl) acetic acid (Compound No. 15 ) This compound is synthesized from the compound described in Preparation 9.1 according to a procedure identical to that described in Preparation 5. 9.3 Preparation of f4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-in-amide of 4 - ((S) -1-carbamoylmethyl-piperidin-3-ylmethyl) -pi peri-di-carboxylic acid To a solution of 0.1 g of the compound described in step 9.2 in 1 mL of DCM, 0 is added, 1 g of TBTU, 0.02 g of HOB t and then 0.08 mL of DI PEA. After 2 hours of stirring at RT, a stream of ammonia is bubbled into the solution for 2 hours. The reaction medium is then filtered, the filtrate is washed with a saturated NaHCO3 solution then with a saturated NaCl solution. After drying over MgSO, the organic phase is concentrated to provide 0.09 g of the crude product. The crude product is purified by flash chromatography on silica gel to give 0.052 g of the expected compound as a white solid. MH + = 555.7 at = 6.68 min PF = 134 ° C Example 10: f4- (S-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl-1-amide of 4-r (S) -1 acid - (2H-tetrazol-5-ylmethyl-piperidin-3-ylmethyl-pi-perazine-1-carboxylic acid (Compound No. 42) 10.1 Preparation of r4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2 4 - ((S) -1-cyanomethyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid -amide (Compound No. 26) To a solution of 0.45 g of the compound obtained in step 1.5 in 4 mL of 1.5 acetone, add 0.1 g of Na2CO3, cool the medium to 0 ° C, then add 0.06 mL of 2-chloroacetonitrile and stir the medium until it returns to RT. to add 0.012 mL of 2-chloroacetonitrile and 0.02 g of Na2CO3 The medium is stirred at RT for 2 hours, then concentrated, the crude product is triturated in water and then extracted in ether. times with a saturated NaHCO3 solution and with a saturated solution of NaCl, after drying over MgSO4 l the organic phase is c concentrate, then purify by flash chromatography on silica gel to give 0.34 g of the expected compound as a white solid. MH + = 537.7 at = 7.67 min PF = 106 ° C 10.2 Preparation of r4- (5-cyclohexyl-2-methoxy-phen-p-thiazole-2-yl-amide of 4-f (S) acid -1 -2H-tetrazol-5-ylmetin-? Iperidin-3-ylmethyl-piperazine-1-carboxylic acid To a suspension of 0.34 g of the compound synthesized in step 10, 1 in a mixture of 3 mL of water and 1 mL of isopropanol, 0.06 g of NaN3 and 0.14 g of ZnBr2 are added.The mixture is heated at 80 ° C for 40 hours, then 0.03 g of NaN3 and 0.07 g of ZnBr2 are added again and the stirring is maintained at 80 ° C for 12 hours. The medium is filtered, the solid is rinsed in water, then in ether. The solid is purified by preparative HPLC to give 56 mg of the expected compound. M H + = 580.7 at = 7.32 min Example 11: r4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-yl-amide of 4 - ((S? -1-phenyl-piperidine -3-ylmethyl) -piperazine-1-carboxylic acid (Compound No. 30) 1 1 .1 Preparation of [a (R) -1-benzyl-4- (piperidin-3-ylmethylpiperazine To a solution of 1.35 g of the compound obtained in stage 1 .2 in 5 mL of dioxane, 20 mL of a 4 M solution of HCl in dioxane is added.The medium is stirred 2 h at RT.The medium is filtered, the solid is rinsed with ether then collected in DCM and treated with 1M soda The organic phase is washed with water, then with a saturated solution of NaCl, After drying over MgSO4, the solution is concentrated to give 1 g of the crude product MH + = 274, 3 at = 5.52 min 11.2 Preparation of (S) -1-benzyl-4 - ((1-phenylpiperidin-3-yl) methyl) piperazine 0.26 g of phenyl trifluoromethanesulfonate, 0, is placed in a tube. 8 g of the amine prepared in step 1.1 in 5.6 mL of NMP.The tube is heated under pressure in a Microwave oven for 30 min at 230 ° C. After returning to RT, the medium is hydrolyzed then extracted into ether. The organic phase is washed with water, then with a saturated solution of NaCl. After drying over MgSO 4, the solution is concentrated to give 0.41 g of the crude product. The solid is purified by flash chromatography on silica gel to give 0.067 g of the expected compound. M H + = 350.3 at = 9.97 min. 11.3 Preparation of (S) -1 - ((1-phenylpiperidin-3-yl) methyl) piperazine To a solution of 0.066 g of the compound obtained in step 1.2. 9 mL of methanol, 0.05 g of 10% Pd / C, 50% wet, is added. The medium is stirred at RT for 48 hours at 10 bar of hydrogen. After filtration on celite, the filtrate is evaporated to give 0.037 g of the desired compound. 11.4 Preparation of 4 - ((S) -1-phenyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid 4- (cyclohexyl-2-methoxy-phenyl) -thiazole-2-yl-amide The procedure is identical to that described in Example 1 starting from 4- (5-cyclohexyl-2-methoxyphenyl) -thiazole-2-amine, described in patent application WO 2004/096798 and of the amine obtained in step 1 1.3. M H + = 574.8 at t = 8, 12 min TABLE! NJ O ül n NJ NJ Ol O Ol Oí NJ NJ Ol O Ol Oí NJ N > Ol O Oí Oí Oí s > NJ NJ Ol O Ol Oí Ol The compounds according to the invention have been the object of pharmacological tests that allow the determination of their modulating effect on the activity of the chemi- ocyte receptors. Chemocytes are low molecular weight proteins that belong to the family of proinflammatory cytokines and are involved in the chemotaxis of leukocytes and endothelial cells. Chemotherapy controls numerous biological processes and is associated with inflammatory disorders that appear during stress, injury or infection; the modulation of the effects of chemokines makes it possible to prevent or treat pathologies such as asthma, arthritis, allergies, autoimmune diseases, atherosclerosis or angiogenesis (C. D, Paavola et al., J. Biol. Chem., 1998, 273, (50 ), 3315J-33165). Among the chemokines, the hMCP-1 (Human Monocyte Chemotactic Protein, which belongs to the group of CC chemokines and which is a natural agonist of the CCR2b receptor) is distinguished. The authors have determined the inhibitory activity of the compounds according to the invention in cells expressing the human CCR2b receptor. The concentration of natural agonist hMCP-1 which inhibits 50% (Cl50) of CCR2b receptor activity is 0.57 nM. The compounds according to the invention have a ClSO generally comprised between 0.1 μM and 0.1 nM, and preferably comprised between 100 nM and 0.1 nM. In Millipore GF / B filter plates (ref MAFBNOB10 or 50), it is contacted for 1 h 30 min at room temperature: 50 μl of compound at 3 x 10"5 M in reaction buffer or cold MCP-1 gamma ( (R &D System) Human Recombinant MCP-1) (final concentration in the compound: 1.05 M), as well as 50 μL of iodinated CP-1 M ([125 |] - Bolton recombinant human MCP-1) + Hunter labeled (Amersham)) at 0.3 nM in distilled water (final concentration in iodinated MCP-1: 0.1 nM), as well as 50 μl of CHO-K1 -CCR2B cells (obtained on Euroscreen Brussels, Belgium) at a rate of 6 x 106 cells / mL (final concentration in reaction buffer: 3 x 105 cells / well) The filters have been pre-saturated with 100 μl of final 0.0125% PEI in PBS for 72 h at 4 ° C and the PEI has been removed by filtration The contents of the wells are filtered and washed twice with the reaction buffer, and the filters are allowed to dry overnight.The next morning, 20 μl / well are distributed the "sparkling Optiphase Super Mix Wallac". The filters are impregnated for 1 to 2 h, then counted in Trilux lode 125.7 min. Reaction buffer = PBS buffer, 50 nM Hepes, 1 mM CaCl2, MgCl25 mM 0.5% BSA without fatty acid, adjusted to pH 7.4. For example, compound n ° 9 has presented an Cl50 of 4 nM, compound n ° 10 has presented an Cl50 of 53 nM, compound n ° 22 has presented an Cl50 of 4 nM, compound n ° 40 has presented a CI5o 1 of 82 nM, compound nß 41 has presented an IC 50, of 39 nM, compound n ° 33 has presented an Cl 50 of 20 nM, compound n ° 1 1 has presented an Cl 50 of 20 nM, compound n ° 23 has presented a C or 8 nM, compound No. 29 has presented a Cl50 of 50 nM and compound No. 45 has presented an Cl50 of 73 nM. The compounds according to the invention can therefore be used for the preparation of medicaments, in particular antagonist drugs for the effect of chemokines. Thus, according to another of its aspects, the present invention relates to medicaments comprising a compound of formula (I), or a salt of addition of the latter to an acid acceptable from a pharmaceutical point of view, or also a hydrate or a solvate These drugs find application in therapy, mainly in the prevention and treatment of different pathologies such as: - acute and chronic immunoinflammatory diseases and syndromes such as atherosclerosis, restenosis, chronic putnamic diseases, in particular COPD (chronic obstructive pulmonary disease) pulmonary disease); respiratory dyspnea syndrome; bronchial hyperactivity; colitis; silicosis; fibrous pathologies, pulmonary fibrosis, cystic fibrosis; viral or bacterial infections, AIDS, meningitis, malaria, leprosy, tuberculosis, herpes, cytomegalovirus infections; septic shock, septicemia, endotoxic shock; graft rejection; bone pathologies such as osteoporosis, osteoarthritis; conjunctivitis; atypical or contact dermatitis; eczema glomerulonephritis; pancreatitis; ulcerative colitis, autoimmune diseases such as rheumatoid polyarthritis, plaque sclerosis, amyotrophic lateral sclerosis, Crohn's disease, lupus erythematosus, scleroderma, psoriasis; Parkinson's disease; Alzheimer disease; diabetes; cachexia; obesity; - treatment of pain, particularly neuropathic and inflammatory; - allergic diseases such as allergic respiratory diseases, asthma, rhinitis, pulmonary hypersensitivity, delayed hypersensitivity; - diseases and disorders in which are involved anigiogenic processes such as cancers (intratumoral angiogenesis), retinal diseases (macular degeneration linked to age: LA DM); - cardiac pathologies: hemodynamic shock; cardiac ischemia; attacks by post-ischemic reinfusion; myocardial infarction, coronary thrombosis, heart failure, angina. According to another of these aspects, the present invention relates to pharmaceutical compositions comprising, as an active ingredient, a compound according to the invention. These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt, a hydrate or solvate of said compound, as well as at least one pharmaceutically acceptable excipient. Said excipients are selected according to the pharmaceutical form and the desired administration mode, among the usual excipients which are known to those skilled in the art. In the pharmaceutical compositions of the present invention, for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration, the active ingredient of formula (I) above, or its salt, solvate or optional hydrate, can be administered in unitary form of administration, mixed with conventional pharmaceutical excipients, to animals and humans for prophylaxis or treatment of the above disorders or diseases. Suitable unit dosage forms comprise oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sub-nual, buccal, intratracheal, intraocular, intranasal, inhalative, administration forms. forms of topical, transdermal, subcutaneous, intramuscular or intravenous administration, forms of rectal administration and implants. For topical application, the compounds according to the invention can be used in creams, gels, ointments or lotions. By way of example, a unitary form of administration of a compound according to the invention in the form of a tablet may comprise the following components: Compound according to the invention 50.0 mg M anitol 223.75 mg Croscarmellose sodium 6.0 mg Corn starch 15 , 0 mg Hydroxypropyl methylcellulose 2,25 mg Magnesium stearate 3,0 mg Orally, the dose of active ingredient administered per day can reach 0, 1 to 1,000 mg / kg, in one or more doses. There may be particular cases in which higher or lower doses are appropriate; and said doses are not outside the scope of the invention. According to the usual practice, the doctor determines the appropriate dose for each patient according to the mode of administration, the weight and the response of said patient. The present invention, according to another of its aspects, also relates to a method for treating the pathologies indicated above, comprising the administration to a patient of an effective dose of a compound according to the invention, or one of its salts, hydrates or pharmaceutically acceptable solvates.

Claims

CLAIMS 1.
Compound of formula (I) below: wherein: RT represents a hydrogen atom, a halogen atom, an alkyl group (C? -8), trifluoroalkyl (C? -C4), -OH, -O-alkyl (d-C8), -O-trifluoroalkyl ( C? -C8), -O-alkyl (C? -C8) -cycloalkyl (C3-C10), -O-cycloalkyl (C3-C10) -O-CH2-CH = CH2, -S-alkyl (C? - C); R2 represents a hydrogen atom, a halogen atom, a -OH group, (C? -C8) alkyl, trifluoroalkyl (C? -C), perfluoroalkyl (C? -C4), cycloalkyl (C3-C10), -O-alkyl (d-C8) -O-alkyl (d-C8) -cycloalkyl (C3-C10), -O-cycloalkyl (C3-C10), -O-CH2-CH = CH2, -alkyl (C? -Cβ) - cycloalkyl (C3-C? o); Y represents a hydrogen atom or a halogen; p represents 2 or 3; - R3 represents: a1) a group of formula - (CH2) a-A in which a represents 1, 2, 3 or 4, and A is selected from the group consisting of: which R7 is selected from the group consisting of • alkyl (C? -C8) -COO-alkyl (C? -8), • -CO-alkyl (C? -8) in which the alkyi is substituted by less a halogen atom, • -cycloalkyl (C3-C10), • phenyl, • -COO-cycloalkyl (C3-C10), • SO2-alkyl (d-C8) in which the alkyl is substituted by at least one atom of halogen, • -SO2-phenyl in which the phenyl is substituted by at least one group -O-alkyl (Ci-β), • SO2-heteroample wherein the heteroaryl is a pyrazole, an isoxazole or an imidazole and in wherein heteroaryl is independently substituted by at least one group selected from halogen or -alkyl (Ci-Cß), • -SO 2 -N ((C 1 -C 8 alkyl)) 2, -SO 2 -OH, -SO 2 -cycloalkyl (C 3) -C10), -CO-NH (alkyl (d-C8)), -alkyl (d-C8) -CN, • -alkyl (C? -8) -imidazole, -alkyl (C? -8) -COOH, -alkyl (C? -C8) -COO "M +, -alkyl (d-C8) -OH, -alkyl (d-C8) -tetrazole, -alkyl (C? -8) -CO-NH2, -alkyl ( C? -C8) -CO-NH (alkyl (C? -C8) )), -alkyl (C? -Cβ) -CO-NH ((C3-C10) cycloalkyl), -alkyl (C? -8) -CO-N ((d-C8) alkyl) (cycloalkyl (C3) -C10)), -alkyl- -alkyl (C? -C8) -CO-N (cycloalkyl (C3-C? 0)) 2, in which M + is an alkali metal cation selected from Li +, Na + and K + , and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different; a2) a group of formula -CO (CH2) b-A wherein b represents 0, 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R7 is as defined above; a3) a group -B where B is selected in the group consisting of: wherein R is as defined above; a4) a group of formula - (CH2) a-C wherein a represents 1, 2, 3 or 4, and C is selected from the group consisting of: wherein: R8 is selected from the group consisting of: • a hydrogen atom, • an alkyl group (C? -8), • alkyl (d-C8) -COO-alkyl (d-C8), • -CO -alkyl (C? -C8) in which the alkyl is optionally substituted by at least one halogen atom, • -cycloalkyl (C3-C? 0), • phenyl, • -COO-cycloalkyl (C3-C10), • -SO2-alkyl (C? -C8) in which the alkyl is optionally substituted by at least one halogen atom, • -SO-phenyl in which the phenyl is substituted by at least one -O-alkyl group (C? -C8), -SO2-heteroaryl in which the heteroaryl is a pyrazole, an isoxazole or an imidazole and in which it is optionally independently substituted by at least one group selected from halogen or -alkyl (d-C8), - SO2-N ((C? -C8 alkyl)), -SO2-OH, -SO2-cycloalkyl (C3-C? O), -CO-NH ((C? -C8) alkyl, -alkyl (C? C8) -CN, -alkyl (C? -C8) -imidazole, -alkyl (C? -C8) -COOH, -alkyl (C? -8) -COO "M \ -alkyl (C? -8) -OH , -alq uilo (C? -C8) -tetrazole, -alkyl (C? -C8) -CO-NH2, -alkyl (d-C8) -CO-NH (alkyl (d-C8)), -alkyl (C? -8 ) -CO-NH ((C3-C10) cycloalkyl), -alkyl (d-C8) -CO-N (alkyl (d-C8)) (cycloalkyl (C3-C10)), -alkyl (C? -C8) -CO-N (alkyl (d-C8)) 2, -alkyl (C? -8) -CO-N (cycloalkyl (C3-C? 0)) 2, wherein M + is an alkali metal cation selected from Li +, Na + and K +, and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different; - R9 is selected from the group consisting of: hydroxyl, O-alkyl (C? -8), -O-trifluoroalkyl (C? -8), -O-alkyl (C? -8) -cycloalkyl (C3-C10) - , O-cycloalkyl (C3-C10), - Ra, Rb, Rc and Rd are independently a hydrogen atom or a methyl group, at least one of Ra, Rb, Rc and Rd being a methyl group; - Re, Rf, Rg and Rh are independently a hydrogen atom or a methyl group; ad) a group of formula -CO (CH2) b-C wherein b represents 0, 1, 2, 3 or 4, and C is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are as defined above, aβ) a group -D in which D is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are as defined above, in the form of base or addition salt to an acid, as well as in the form of hydrates or solvates 2.
Compound according to claim 1, of formula (1a) below: (the) wherein Ri, R2, R3 and Y are as defined in claim 1.
Compound according to claim 2, of formula (la.) characterized in that R1 is in position 2 and R2 is in position
5. 4. Compound according to any of claims 1 to 3, characterized in that R1 represents -O-alkyl (C? -8). 5. Compound according to any of claims 1 to 4, characterized in that R2 represents an alkyl group (C? -C8), cycloalkyl (C3-C10), perfluoroalkyl (C1-C4) or -O-alkyl (d-C8).
6. Compound according to claim 5, characterized in that R2 represents an alkyl group (C? -C8), cycloalkyl (C3-C10) or -O-alkyl (C? -8). Compound according to any of claims 1 to 6, characterized in that R3 represents a group formula - (CH2) a-A in which a represents 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R
7, Ri, R2, Y and p are as defined in claim 1
8. Compound according to any of claims 1 to 6, characterized in that R3 represents a group of formula -CO (CH2) bA wherein represents 0, 1, 2, 3 or 4, and A is selected from the group consisting of: wherein R7, Ri, R2, Y and p are as defined in claim 1.
9. The compound according to any of claims 7 or 8, characterized in that A is selected from the group consisting of: wherein Ri, R2, Y and p are as defined in claim 1.
10. Compound according to any of claims 1 to 6, characterized in that R3 represents a group -B in which B is selected from the group consisting of: wherein R7, Ri, R? 2 l Y and p are as defined in claim 1
1 1. Compound according to any of claims 1 to 10, characterized in that R7 is selected from the group consisting of: • -alkyl (C? -C8) -COO-alkyl (C? -8), • -CO-alkyl (C? C8) in which the alkyl is substituted by at least one halogen atom, • -cycloalkyl (C3-C10), • phenyl, • -SO2-alkyl (d-C8) in which the alkyl is substituted by at least one halogen atom, • -SO2-phenyl in which the phenyl is substituted by at least one -O-alkyl group (C? -8), • -heteroaryl-SO? wherein the heteroaryl is a pyrazole or an isoxazole or an imidazole and wherein heteroaryl is independently substituted by at least one group selected from halogen or -alkyl (C? -8), • -SO2-N (alkyl (C ? -C8)) 2, -SO2-OH, -CO-NH (alkyl (d-C8)), -alkyl (C? -8) -CN, -alkyl (C? -8) -COOH, -alkyl ( C? -C8) -COO-M +, -alkyl (d-C8) -OH, -alkyl (C? -8) -tetrazole, -alkyl (d-C8) -CO-NH2, wherein M + is a alkali metal cation selected from Li +, Na + and K +, and when there are two alkyl or cycloalkyl substituents attached to the nitrogen atom, they can be independently identical or different.
12. Compound according to any of claims 1 to 10, characterized in that R7 represents -SO2-cycloalkyl (C3-)
13. Compounds according to any of claims 1 to 12, chosen from: [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1-cyclopropyl-pi peri-di-3-ylmethyl) - piperazine-1-carboxylic acid, 4- (1-isopropylcarbamoyl-piperidin-3-yl) -piperazine-1-carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (1-cyclopropanesulfonyl-piperidin-4-yl) -piperazine-1-carboxylic acid ethyl ester 3 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl}. -piperidin-1-yl ) -propionic acid, 3 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -ti-azol-2-ylcarbamoyl] -piperazin-1-ylmethyl}. -piperidin-1-yl) -propionic acid ethyl ester 4 - ((R) -3-. {4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] - piperazin-1-ylmethyl.}. -piperidin-1-yl) -butyric acid, 4 - ((R) -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole- 2-ylcarbamoyl] -piperazin-1-ylmethyl.}. -piperidin-1-yl) -butyric ester ethyl ester of 5 - ((R) -3- acid. { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl} -piperidin-1-yl) -pentanoic acid, 5 - ((R) -3-. {4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazole-2-ylcarbamyl] - pi perazin-1-ylmethyl] -piperidin-1-yl) -pentanoic acid, 4-cyclohexyl [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide l-pi perazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahi dro-pyran-4-i I) -pi perazi na-1-carboxylic acid, 14.
Compound characterized in that it is: 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-) il) -piperazine-1-carboxylic acid, 15.
Compounds according to any of claims 1 to 12, selected from: [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of the acid - ((S) -1-Cyclopropyl-piperidin-3-ylmethyl) -pi perazi-na-1-carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] 4- (tetrahydro-pyran-4-carbonyl) -piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) - 1 -carbamoi methyl-piperidin-3-ylmethyl) -pi perazi na-1-carboxylic acid ((S) -3-. { 4- [4- (5-cyclohexyl-2-methoxy-f-enyl) -thiazole -2-i Icarbamoyl I] -pi perazine n-1-ylmethyl} -pi peri di n-1-yl) -acetic, 4- (5-cyclohexyl-2-methoxy-phenyl) -5-fluoro-thiazol-2-yl] -amide of 4 - ((S) - 1) -cyclopropyl-pi peri-di-3-yl methyl) -pi perazi-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- ( tetrahydro-pyran-4-l methyl) -p-perazi-na-1-carboxylic acid ((S) -3-. {4- [4- (5-cyclohexyl-2-methoxy-phenyl) - ethyl ester) ti azol -2-i I carbamoyl l-pi perazin-1-lylmethyl.]. -pi peri di n-1 -i I) -acetic, [4- (5-cyclohexyl-2-methoxy-phenyl) - thiazol-2-yl] -amide of 4 - [(R) -1 - (2-cyano-ethyl) -piperidin-3-ylmethyl] -piperazine-1-carboxylic acid, sodium salt of 3 - ((R)) acid -3- { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -piperazin-1-ylmethyl] -piperidin-1-yl) -propionic acid, [4]. - (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(R) -1 - (2-carbamoyl-1-ethyl) -pi peri-di-3-yl) meti l] -pi perazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((R) -1 -cicl opropi lp i peri di n-3-carboni I) -pi perazi na-1-carboxylic acid, 4- (5-butyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S)) -1-cyclopropyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid, 4- (5-cyclopentyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) - 1-cyclopropyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid, 4- (5-butyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S)) -1-cyclopropyl-piperidin-3-ymethyl) -piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) - 1-cyanomethyl-1-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((R) -) 1-cypropyl-pi-peri-di-3-i-I) -pi perazi-na-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide 4- (1-cyclic opropi I-pi peri di n-4-i I) -p-perazi na-1 -carboxylic acid[4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1-cid-opropanesulfonyl-pi peri-di-n-3-i-meti I) -pi perazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - ((S) -1-phenyl-pi) peri n -3-i I meti) -pi perazi na-1-carboxylic acid, 2-. { 4- [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-ylcarbamoyl] -pi perazi n-1-ylmethyl} -piperidin-1-sulfonic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(S) -1 - (2-hydroxy-ethyl) -pi] peridin-3-ylmethyl] -pi perazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4 - [(S) -1 - ( 2, 2, 2-trifluoro-acetyl) -piperidin-3-ylmethyl] -pi perazi na-1 -carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -5-fluoro-thiazol-2-yl ] 4- (tetrahydro-pi ran-4-yl) -pi perazi na-1-carboxylic acid amide, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl-amide acid] 4 - ((S) -1-Di methylsulfonyl-piperidin-3-ylmethyl) -piperazine-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide 4 - [(S) -1 - (2 H -tetrazol-5-ylmethyl) -piperidin-3-yl] methyl] -pi perazine na-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy 4- [1- (5-chloro-1,3-dimethyl-1 H -pyrazol-4-sulfonyl) -piperidin-2-ylmethyl] -piperazine-1-phenyl] -thiazol-2-yl] -amide. -carboxylic acid [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- [1 - (1,3-dimethyl-1 H- pyrazol-4-sulfonyl) -piperidin-2-ylmethyl] -pi perazi na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- [ 1 - (1, 5-dimethyl-1 H-pi-razol-4-sulfonyl) -pi peri di n-2-i I-methyl] -pi perazi na-1 -carboxylic, [4- (5-cyclohexyl- 4- [1- (1-methyl-1 H -pyrazol-4-sulfonyl) -piperidin-2-ylmethyl] -pi perazine naphthalene-2-methoxy-phenyl) -thiazol-2-yl] -amide. -carboxylic acid 4- [1 - (5-m ethyl-isoxazole-4-sulfonyl) -pi peri di [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide. n-2-i I meti I] -piperazine-1-carboxylic acid, 4- [1 - (1-methyl) [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] -1 H-imidazol-4-sulfonyl) -piperidin-2-ylmethyl] -pi perazi-na-1-carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of the 4- (1-di meti I sulfisoi l-pi peri di n-2-i I meti I) -pi perazi na-1 -carboxylic acid, [4- (5-cyclohexyl-2-methoxy-phenyl) - thiazol-2-yl] -amide of 4- [1- (2,2,2-trifluoro-ethanesulfonyl) -piperidin-2-ylmethyl] -pip erazin-1-carboxylic acid, 4- [1 - (4-methoxy-benzenesulfonyl) -piperidin-2-ylmethyl] 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] -piperazine-1-carboxylic acid, 4- (5-cyclopentyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazine-1-carboxylic acid, [4- (3, 5-dimethyl-isoxazole-4-sulfonyl) -piperidin-2-ylmethyl] 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide] -pi perazi na-1-carboxylic acid, 4- (5-butyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -piperazi na- 1 -carboxylic acid, 4 - [(S) -1 - (1-methyl-1H-imidazole-4-sulfonyl [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide. ) -piperidin-3-ylmethyl] -piperazine-1-carboxylic acid, 4- (5-cyclohexyl-2-ethoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-) i I) -pi perazi na-1-carboxylic acid, 4- (5-cyclopentyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro-pyran-4-yl) -pi perazi na-1 -carboxylic, [4- (5-butyl-2-methoxy-phenyl) -t iazol-2-yl] -amide of 4- (tetrahydro-pi ran-4-i) -pi perazine na-1-carboxylic acid, [4- (2-methoxy-5-propoxyphenyl) -thiazole-2-yl] ] 4- (tetrahydro-pyran-4-yl) -pi perazi-na-1-carboxylic acid amide, [4- (5-propyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of the acid 4- (tetrahydro-pyran-4-yl) -pi perazi-na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (tetrahydro- pyran-4-yl) - [1,4] diazepane-1-carboxylic acid, 16.
Compound according to any of claims 1 to 6, characterized in that R3 represents a group of formula - (CH2) aC in which a represents 1 , 2, 3 or 4, and C is selected from the group consisting of: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R,, R2, Y, and p are as defined in claim 1. 7.
The compound according to any of claims 1 to 6, characterized in that R3 represents a group of formula -CO (CH2) bC wherein b represents 0, 1, 2, 3 or 4, and C is selected from the group Constituted by: wherein R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, R1 f R2, Y and p are as defined in claim 1.
18. Compound according to any of claims 1 to 6, characterized in that R3 represents a group -D in which D is selected from the group consisting of: where R8, R9, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, RL R2 | Y and p are as defined above.
19. Compounds according to any of claims 16 to 18, selected from: 4- (1,1-dioxo-hexahydro-1) -4- (cyclohexyl-2-methoxy-phenyl) -thiazole-2-amide 6-Thiopyran-4-yl) -piperazine-1-carboxylic acid, 4- (4-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (4-hydroxy-cid) ohexi I) -pi perazi na-1-carboxylic acid, 4- (1-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of the acid 4- (1, 2, 2, 6, 6 pentamethyl-piperidin-4-yl) -pi perazi na-1-carboxylic acid, 4- (2-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (2, 2, 6) , 6-tetramethyl-piperidin-4-yl) -pi perazi-na-1-carboxylic acid, 4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] -amide of 4- (2, 2-di m eti I -tetrahi dro-pyran-4-i I meti I) -pi perazi na-1-carboxylic, [4- (5-cyclohexyl-2-methoxy-phenyl) -thiazol-2-yl] - 4- (Tetrahy dro-ti opyran-4-I) -pi perazine na-1-carboxylic acid amide,
20. Process for the preparation of a compound of the formula (I) according to any of the claims 1 to 19, comprising the step of reacting a compound of formula (II) with an amine derivative of formula (III) OH) wherein R, R2, Y, R3 and p are as defined in claim 1 and R3 represents a precursor group of R3 or a group R3 as defined in claim 1, in the presence of a coupling agent and in a solvent such as dichloromethane, dimethylformamide or toluene, in the presence of a base such as triethylamine or K2CO3, at a temperature ranging from 0 ° C to 100 ° C.
21. Process for the preparation of a compound of formula (I) according to any of claims 1 to 19, comprising the step of reacting the compound of formula (IX), in which R ^ R2, Y, Ra and p are as defined in claim 1, with a compound of formula (Vl) or (V.2) or (VI. 1) or (VI.2) or (Vil.1) or (Vil.2) or a ketone B 'or D', wherein a and b are as defined in claim 1, and A ', B', C and D 'represent respectively a precursor group of A, B, C or D, or a group A, B, C or D as defined in claim 1, (IX) X- (CH,) .. A '(Vil 1) (I) X-íCHjJ.-C' (Vil 2) B- cr in order to obtain a compound of formula (I) in which R'3 represents a precursor group of R3 or a group R3 as defined in claim 1.
22. Medicament, characterized in that it comprises a compound of the formula (I) ) according to any one of claims 1 to 19, or an addition salt of this compound to a pharmaceutically acceptable acid, or, even, a hydrate or a solvate of the compound of formula (I).
23. Pharmaceutical composition, characterized in that it comprises a compound of formula (I) according to any of claims 1 to 19, or a pharmaceutically acceptable salt, a hydrate or a solvate of this compound, as well as at least one pharmaceutically acceptable excipient.
24. Use of a compound of formula (I) according to any of claims 1 to 19 for the preparation of a medicament for the treatment or prevention of diseases and acute or chronic immunoinflammatory syndromes, such as atherosclerosis, allergic diseases as well as diseases in those that are involved angiogenic processes.
25. Use of a compound of formula (I) according to claim 24 for the preparation of a medicament for the treatment or prevention of cancers in which anigiogenic processes are involved.
26. Use of a compound of formula (I) according to any of claims 1 to 19 for the preparation of a medicament for the treatment or prevention of viral or bacterial diseases, cardiac pathologies or obesity.
27. Use of a compound of formula (I) according to any of claims 1 to 19 for the preparation of a medicament for the treatment or prevention of diseases linked to a modulation of the activity of the CCR2b receptor.