Patent EA-003093-B1 (EA)
Title: Carboxamidothiazole derivatives, preparation, pharmaceutical compositions containing them
Inventor: BRODIN ROGER
IPC: C07D417/04
Filed: 1998-09-18
Abstract: 1. Compound of formula:   in which: R6a is a chlorine or a methyl; R10, R11 and R13 are independently of each other, hydrogen, methyl, ethyl, hydroxyl, acetyloxy, methoxy, ethoxy, methylthio, trifluoromethyl or amino group or a halogen; with the limitation that one or two of the substituents R10, R11 and R13 are other than hydrogen; as well as the salts and solvates thereof. 2. Compound according to Claim 1, of formula:   in which: one or two of the substituents R10a, R11a and R13a are a methyl, a methoxy, a chlorine, a fluorine or a trifluoromethyl, the other(s) being hydrogen, as well as the salts and solvates thereof. 3. Compound according to Claim 2, chosen from: 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-methylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5,7-dimethylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4-methoxyindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4-methylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4,5-dimethylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-methoxyindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-chloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4,5-dichloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4,7-dimethylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4,5-dimethoxyindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-7-methoxyindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-7-methylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5,7-dichloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4,7-dimethoxyindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-methoxy-7-methylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-methyl-7-chloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-chloro-7-methylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-chloro-7-fluoroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4-methyl-7-chloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4-methyl-5-chloroindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-chloro-7-trifluoromethylindole-1-acetic acid; 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-4-methoxy-7-methylindole-1-acetic acid; as well as the salts and solvates thereof. 4. Compound according to Claim 3, wherein the compound is 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5-methylindole-1-acetic acid, as well as the salts and solvates thereof. 5. Compound according to Claim 3, wherein the compound is 2-(4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)thiazol-2-ylcarbamoyl)-5,7-dimethylindole-1-acetic acid, as well as the salts and solvates thereof. 6. A process for the preparation of a compound of formula (Ib) according to Claim 1, and salts and solvates thereof, which comprises the following steps: a) condensation a 2-aminothiazole of formula:   in which: R1 is a substituted phenyl group of formula:   with R6 being a chlorine or a methyl and R2 is   with an acid of formula: R'3COOH, in which R'3 is a functional derivative of   with a protected form of the said acid function, and R10, R11 and R13 being as defined in Claim 1; b) converting the compound thus obtained into a compound of formula (Ib) by deprotection of the protected acid function; and c) isolating the compound of formula (Ib) thus obtained, in its current form or in the form of one of the salts or solvates thereof. 7. A pharmaceutical composition containing an effective dose of at least one compound of formula (Ib) according to any of Claim 1-5, or one of the pharmaceutically acceptable salts, solvates or hydrates thereof. 8. A use of compound according to any of Claim 1-5 for obtaining medicaments for combating diseases whose treatment requires stimulation of the cholecystokinin CCK-A receptors. 9. A use according to Claim 8 for obtaining medicaments for treatment of disorders of the gastrointestinal system. 10. A use according to Claim 8 for obtaining medicaments for treatment of disorders of the central nervous system. 11. A use of compound according to any of Claim 1-5 for obtaining medicaments suitable for treatment of obesity. 12. A use of compound according to any of Claim 1-5 for obtaining medicaments suitable for treatment of irritable colon syndrome. 13. A use of compound according to any of Claim 1-5 for obtaining medicaments suitable for treatment of dyskinesia.