Patent ID: 6414012
Filing Date: 2002-07-02
Classification: A61K,A61P,C07D,Y10S

Abstract:
A method for inhibiting lipoperoxidation in a host for the prophylaxis or treatment of arteriosclerosis, diabetes, hyperlipemia, or cerebrovascular or cardiovascular ischemic diseases in said host comprising contacting said host with a heterocyclic compound of the formula (I) whereinone of R1, R2, R3, and R4 is a group of the formula â€”NHCOâ€”R6 wherein R6 is selected from the group consisting of C1-C12 alkyl, cyclo C3-C6 alkyl, cyclo C3-C6 alkyl C1-C3 alkyl, phenyl, naphthyl, phenyl C1-C4 alkyl, naphthyl C1-C4 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C1-C8 alkyl, piperidyl C1-C8 alkyl, piperidino C1-C8 alkyl, morpholinyl C1-C8 alkyl, morpholino C1-C8 alkyl, piperazinyl C1-C8 alkyl, pyrrolyl C1-C8 alkyl, imidazolyl C1-C8 alkyl, and pyridyl C1-C8 alkyl (wherein any of the foregoing is optionally substituted with a C1-C4 alkyl, amino, hydroxy, di(C1-C4)alkylamino, C1-C4 aminoalkyl, C1-C4 alkoxy, carboxyl, C1-C4 alkoxycarbonyl, C1-C4 carboxyalkyl, C2-C5 acyloxy, phenyl, phenoxy, halogen, (C1-C4)alkyl phenyl(C1-C4)alkylamino, or di[phenyl(C1-C4)alkyl]amino), â€”RASO3A, and â€”RBPO3B where RA and RB are each C1-C8 alkylene and A and B are each alkali metal or hydrogen atom, â€”NR7R8 where R7 is selected from the group consisting of C1-C12 alkyl, cyclo C3-C6 alkyl, cyclo C3-C6 alkyl C1-C3 alkyl, phenyl, naphthyl, phenyl C1-C4 alkyl, and naphthyl C1-C4 alkyl (wherein any of the foregoing is optionally substituted with a C1-C4 alkyl, amino, hydroxy, di(C1-C4)alkylamino, C1-C4 aminoalkyl, C1-C4 alkoxy, carboxyl, C1-C4 alkoxycarbonyl, C1-C4 carboxyalkyl, C2-C5 acyloxy, phenyl, phenoxy, halogen, (C1-C4)alkyl phenyl(C1-C4)alkylamino, or di[phenyl(C1-C4)alkyl]amino), and R8 is hydrogen atom or C1-C4 alkyl, and â€”R9â€”OCOR10 where R9 is C1-C8 alkylene and R10 is selected from the group consisting of C1-C12 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C1-C8 alkyl, piperidyl C1-C8 alkyl, piperidino C1-C8 alkyl, morpholinyl C1-C8 alkyl, morpholino C1-C8 alkyl, piperazinyl C1-C8 alkyl, pyrrolyl C1-C8 alkyl, imidazolyl C1-C8 alkyl, and pyridyl C1-C8 alkyl (wherein any of the foregoing is optionally substituted with a C1-C4 alkyl, amino, hydroxy, C1-C4 dialkylamino, C1-C4 aminoalkyl, C1-C4 alkoxy, carboxyl, C1-C4 alkoxycarbonyl, C1-C4 carboxyalkyl, C2-C5 acyloxy, phenyl, phenoxy, halogen, (C1-C4)alkyl phenyl(C1-C4)alkylamino, or di[phenyl(C1-C4)alkyl]amino), and the remaining three of R1, R2, R3, or R4 may be the same or different and each is independently a hydrogen atom, a C1-C4 alkyl or a C1-C4 alkoxy; R5 is selected from the group consisting of C1-C12 alkyl, cyclo C3-C6 alkyl, cyclo C3-C6 alkyl C1-C3 alkyl, phenyl, naphthyl, phenyl C1-C4 alkyl, naphthyl C1-C4 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C1-C8 alkyl, piperidyl C1-C8 alkyl, piperidino C1-C8 alkyl, morpholinyl C1-C8 alkyl, morpholino C1-C8 alkyl, piperazinyl C1-C8 alkyl, pyrrolyl C1-C8 alkyl, imidazolyl C1-C8 alkyl, and pyridyl C1-C8 alkyl (wherein any of the foregoing is optionally substituted with a C1-C4 allyl, amino, hydroxy, C1-C4 dialkylamino, C1-C4 aminoalkyl, C1-C4 alkoxy, carboxyl, C1-C4 alkoxycarbonyl, C1-C4 carboxyalkyl, C2-C5 acyloxy, phenyl, phenoxy, halogen, (C1-C4)alkyl phenyl(C1-C4)alkylamino, or di[phenyl(C1-C4)alkyl]amino), C2-C5 alkenyl, C2-C8 alkynyl, a and di(C1-C8 )alkylamino(C2-C8)acyloxy(C1-C8 )alkyl, â€”RDSO3D â€”REPO3E where RD and RE are each C1-C8 alkylene and D and E are each alkali metal or hydrogen atom, and m is 1, or a pharmaceutically acceptable salt thereof, with the proviso that R5 is not ethyl when R1, R3, and R4 are hydrogen atom, R2 is (4-methylpentanoyl)amino, and m is 1.