Patent EA-003430-B1 (EA)
Title: Substituted piperazones and their therapeutic uses
Inventor: YUE CHROSTOPHE
IPC: A61P7/02
Filed: 1999-07-16
Abstract: 1. Compounds of general formula (I): in which: R1 is chosen from hydrogen, a C1-C4 alkyl group and a phenyl (C1-C4 alkyl) group; R2 is chosen from hydrogen, a hydroxyl group and a protecting group for the amidino group; R3 is chosen from the groups of formula: -NH-CO-R6, R6 being chosen from C1-C4 alkoxy, C3-C7 cycloalkoxy, benzyloxy, methoxyphenyl, dimethoxyphenyl, benzodioxolyl and benzodioxanyl groups, and the groups of formula: -NH-SO2-R7, R7 being chosen from: - C1-C5 alkyl groups optionally substituted with one or more groups chosen from halogens, hydroxyl groups and the trifluoromethyl group; - mono- or bicyclic C3-C14 cycloalkyl groups; - mono-, bi- or tricyclic C6-C14 aryl groups; - heteroaryl groups chosen from pyridyl, thienyl, quinolyl, benzodioxanyl, benzodioxolyl and isoxazolyl groups; - phenyl (C1-C4) alkyl and naphthyl (C1-C4) alkyl groups; - and the groups of formula: in which n = 1, 2 or 3; the aryl or heteroaryl groups of R7 optionally being substituted with one or more groups chosen independently from halogens, C1-C4 alkyl, trifluoromethyl, C1-C4alkylthio, C1-C4 alkyloxy, C1-C4 alkylsulphonyl, nitro, di((C1-C4)alkyl)amino, phenyl, naphthyl and heteroaryl groups chosen from thienyl, furyl and pyridyl groups, and from groups -COOR, -CH2-COOR or -O-CH2COOR, R being a C1-C4 alkyl group. R4 and R5 are chosen, independently of each other, from hydrogen, a C1-C5 alkyl group or form, together with the nitrogen atom, a group chosen from piperidyl and morpholinyl groups, and the oxo group is in position 2 or 3 on the piperazine; and the addition salts thereof with pharmaceutically acceptable acids. 2. Compounds according to Claim 1, in which R3 is a group -NH-SO2-R7. 3. Compounds according to Claim 2, in which R7 is chosen from phenyl and tolyl groups. 4. Compounds according to Claim 3, which are chosen from ethyl (2S) -3- {[2-(4-{4-[amino(imino)methyl]phenyl}-2-oxopiperazino)acetyl]amino}-2-[(phenylsulphonyl)amino]-propanoate; (2S) -3-{[2-(4-{4-[amino(imino)methyl]-phenyl}-2-oxopiperazino)acetyl]amino}-2-[(phenyl-sulphonyl)amino]propanoic acid, (2S) -3-{[2- (4-{4- [amino [(ethoxycarbonyl) imino]methyl] phenyl}-2-oxopiperazino)acetyl] amino}-2-{[phenyl-sulphonyl]amino}propanoic acid, ethyl (2S) -3-{[2- (4-{4- [imino (morpholino)methyl] phenyl}-2-oxopiperazino)acetyl]amino}-2-{[4-toluenesulphonyl]amino}propanoate, (2S)-3-{[2-(4-{4-[amino(imino)methyl]phenyl}-2-oxo-piperazino)acetyl]amino}-2-{[4-toluenesulphonyl]-amino}propanoic acid, and the addition salts thereof with pharmaceutically acceptable acids. 5. Process for preparing compounds of formula (I) according to Claim 1, by: a) reacting an acid of formula in which Z is a precursor group of a group with an amine of formula to give a compound of formula and b) converting the group Z into a group 6. Therapeutic composition which comprises, as active principle, a compound according to any one of Claims 1 to 4. 7. Use of a compound according to any one of Claims 1 to 4, for the manufacture of an antithrombotic medicinal product. 8. Process for inhibiting the binding of fibrinogen to the blood platelets of mammals, comprising the administration of an effective amount of a compound according to Claim 1. 9. Process for inhibiting the aggregation of blood platelets in a patient, comprising the administration to this patient of an effective amount of a compound according to Claim 1. 10. Process for treating a thrombosis in a patient, comprising the administration to this patient of an effective amount of a compound according to Claim 1. 11. Process for preventing the risk of thrombosis in a patient, comprising the administration to this patient of an effective amount of a compound according to Claim 1.