Patent EA-004042-B1 (EA)
Title: New aminopyrroline compounds, process for preparation and pharmaceutical compositions comprising them
Inventor: BOUSQUET PASCAL
IPC: C07D209/40
Filed: 2000-11-16
Abstract: 1. A compound selected from those of formula (1): in which: n is 1 or 2, X represents alkylene, alkenylene or alkynylene, optionally substituted arylene, or optionally substituted heteroarylene, R10 represents hydrogen or a linear or branched (C1-C6)alkyl and R11, and R12 together form a bond, or alternatively R12 represents hydrogen or linear or branched (C1-C6)alkyl and R10 and R11 together form a bond, R2, R3 and R4 each independently of the others represents hydrogen, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)hydroxyalkyl, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)alkoxycarbonyl, optionally substituted aryl, optionally substituted arylalkyl in which the alkyl moiety is linear or branched and has from 1 to 6 carbon atoms, or optionally substituted aryloxyalkyl in which the alkyl moiety is linear or branched and has from 1 to 6 carbon atoms, or alternatively two of R2, R3 and R4, with the carbon atoms carrying them, form a (C5-C7)cycloalkyl group, wherein: - the term alkylene denotes a linear or branched divalent group containing from 1 to 6 carbon atoms, - the term alkenylene denotes a linear or branched divalent group containing from 2 to 6 carbon atoms and from 1 to 3 double bonds, - the term alkynylene denotes a linear or branched divalent group containing from 2 to 6 carbon atoms and from 1 to 3 triple bonds, - the term aryl represents phenyl or naphthyl, and the term arylene represents a divalent group of the same type, - the term heteroaryl denotes a mono- or bi-cyclic unsaturated or partially unsaturated group having from 4 to 11 ring members and from 1 to 5 hetero atoms selected from nitrogen, oxygen and sulphur, and the term heteroarylene represents a divalent group of the same type, - the term substituted associated with the expressions aryl, arylene, arylalkyl, aryloxy-alkyl, heteroaryl and heteroarylene means that the groups in question are substituted in the aromatic moiety by one or more groups selected from halogen, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkoxy, hydroxy, cyano, nitro or amino (optionally substituted by one or two linear or branched (C1-C6)alkyl), its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 2. A compound of claim 1 in which X represents optionally substituted arylene or optionally substituted heteroarylene its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 3. A compound of claim 1 in which X represents alkylene, alkenylene or alkynylene, its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 4. A compound of claim 1 in which R11 and R12 together form a bond its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 5. A compound of claim 1 in which each of R2, R3 and R4 represents hydrogen. 6. A compound of claim 1 in which X represents alkylene or optionally substituted arylene, R10 represents hydrogen or linear or branched (C1-C6)alkyl, R11, and R12 together form a bond, and R2, R3 and R4 each independently of the others represents hydrogen, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)hydroxyalkyl, linear or branched (C1-C6)alkoxycarbonyl, linear or branched (C1-C6)alkoxy, optionally substituted aryl, or optionally substituted aryloxyalkyl in which the alkyl moiety is linear or branched and has from 1 to 6 carbon atoms, its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 7. A compound of claim 1 which is N-(2-cyclopropylphenyl)-3,4-dihydro-2H-pyrrol-5-amine, and addition salts thereof with a pharmaceutically acceptable acid. 8. A compound of claim 1 which is N-(dicyclopropylmethyl)-3,4-dihydro-2H-pyrrol-5-amine, and addition salts thereof with a pharmaceutically acceptable acid. 9. A compound of claim 1 which is N-(2-Cyclopropylpheryl)-2-methyl-3,4-dihydro-2H-pyrrol-5-amine, and addition salts thereof with a pharmaceutically acceptable acid. 10. A method for preparation of compounds of formula (I) according to claim 1, characterized in that mother compound of formula (II) in which of R2, R3 and R4 have values, defined for formula (I), R'12 is hydrogen atom or linear or unbranched (C1-C6) alkyl group, and A is oxygen atom or sulphur atom, is subjected after methylation to reaction with amine of formula (III) wherein n and X have values defined for formula (I), and R'10 is hydrogen atom or linear or unbranched (C1-C6) alkyl group, with the resulting in medium of base of compound of formula (I), which - if necessary is cleaned according to traditional cleaning methods, - if necessary is separated on stereoisomers by traditional methods of separation, - if necessary is transformed in addition salts with pharmaceutically acceptable acid or base. 11. A pharmaceutical composition comprising as an active principle at least one compound of any of claims 1-9, solely or together with one or more pharmaceutically acceptable excipients or vehicles. 12. Use of pharmaceutical composition according to claim 11 in production of medicine for treating a cardiovascular disease. 13. Use according to claim 12 in production of medicine for treating arterial hypertension. 14. Use according to claim 12 in production of medicine for treating arrhythmia.