Patent EA-003511-B1 (EA)
Title: Piperazinone derivatives and their uses
Inventor: YUE CHRISTOPHE
IPC: A61K31/495
Filed: 1999-07-16
Abstract: 1. Compounds of general formula (I): in which: R1 is chosen from hydrogen, a C1-C4alkyl group and a phenyl (C1-C4alkyl) group; R2 is chosen from hydrogen, a hydroxyl group and a protecting group for the amidino group; R3 is chosen from hydrogen, -C1-C5alkyl, C3-C12mono- or bicyclic cycloalkyl, C2-C4alkenyl and C2-C4alkynyl groups, these groups optionally being substituted with groups chosen from halogens and the hydroxyl group; - mono-, bi- or tricyclic C6-C14aryl groups, - heteroaryl groups chosen from pyridyl, thienyl, furyl, quinolyl, benzodioxanyl, benzodioxolyl, benzothienyl, benzofuryl and pyrazinyl groups; - phenyl (C1-C4)alkyl and naphthyl(C1-C4)alkyl groups optionally substituted on the aryl nucleus, and piperonyl groups, R4 and R5 are chosen, independently of each other, from hydrogen and a C1-C5alkyl group, or form, together with the nitrogen atom, a group chosen from piperidyl and morpholinyl groups, aryl and heteroaryl groups optionally being substituted with one or more groups chosen independently from halogens, C1-C4alkyl, trifluoromethyl, C1-C4alkylthio, C1-C4alkylsulphonyl, C1-C4alkyloxy, nitro and groups -COOR, -CH2COOR and -O-CH2-COOR, R being a C1-C4alkyl group, 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, which are chosen from ethyl 3-{[2-(4-{4-[amino(hydroxyimino)methyl]phenyl}-2-oxopiperazino)acetyl]amino}-3-(1,3-benzodioxol-5-yl)propanoate, ethyl 3-([2-(4-{4-[amino(hydroxy-imino)methyl]phenyl}-2-oxopiperazino)acetyl]amino-5-phenylpentanoate, 3-{[2-(4-(4-[amino(imino)methyl]phenyl}-2-xopiperazino)acetyl]amino}-3-(1,3-benzodioxol-5-yl)propanoic acid and the addition salts thereof with pharmaceutically acceptable acids. 3. Process for preparing the compounds of formula I according to Claim 1, by a) reacting an acid of formula II in which Z is a precursor group of a group with an amine of formula III in which R'1 is a C1-C4alkyl or phenyl(C1-C4alkyl) group, to give a compound of formula IV b) converting the group Z into a group and c) optionally, converting the group R'1 into a hydrogen atom. 4. Therapeutic composition which comprises, as active principle, a compound as defined in Claim 1 or Claim 2. 5. Use of a compound as defined in Claim l, or Claim 2, for the manufacture of an antithrombotic medicine. 6. Process for inhibiting the binding of fibrinogen to blood platelets in a mammal, comprising the administration to this mammal of an effective amount of a compound according to Claim 1 or Claim 2. 7. 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 or Claim 2. 8. 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 or Claim 2. 9. 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 or Claim 2.