Patent ID: 6127403
Filing Date: 2000-10-03
Classification: A61K,A61P,C07D,Y10S

Abstract:
A method for inhibiting acyl-CoA:cholesterol acyltransferase in a host in need thereof 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) ##STR43## wherein one of R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is a group of the formula --NHCO--R.sup.6 wherein R.sup.6 is selected from the group consisting of C.sub.1 -C.sub.12 alkyl, cyclo C.sub.3 -C.sub.6 alkyl, cyclo C.sub.3 -C.sub.6 alkyl C.sub.1 -C.sub.3 alkyl, phenyl, naphthyl, phenyl C.sub.1 -C.sub.4 alkyl, naphthyl C.sub.1 -C.sub.4 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C.sub.1 -C.sub.8 alkyl, piperidyl C.sub.1 -C.sub.8 alkyl, piperidino C.sub.1 -C.sub.8 alkyl, morpholinyl C.sub.1 -C.sub.8 alkyl, morpholino C.sub.1 -C.sub.8 alkyl, piperazinyl C.sub.1 -C.sub.8 alkyl, pyrrolyl C.sub.1 -C.sub.8 alkyl, imidazolyl C.sub.1 -C.sub.8 alkyl, pyridyl C.sub.1 -C.sub.8 alkyl, wherein any of the foregoing is optionally substituted with a C.sub.1 -C.sub.4 alkyl, amino, hydroxy, di(C.sub.1 -C.sub.4)alkylamino, C.sub.1 -C.sub.4 aminoalkyl, C.sub.1 -C.sub.4 alkoxy, carboxyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 carboxyalkyl, C.sub.2 -C.sub.5 acyloxy, phenyl, phenoxy, halogen, or phenyl di (C.sub.1 -C.sub.4) alkylamino, --R.sup.A SO.sub.3 A, --R.sup.3 PO.sub.3 B where R.sup.A and R.sup.B are each alkylene and A and B are each alkali metal or hydrogen atom, --NR.sup.7 R.sup.8 where R.sup.7 is selected from the group consisting of C.sub.1 -C.sub.12 alkyl, cyclo C.sub.3 -C.sub.6 alkyl, cyclo C.sub.3 -C.sub.6 alkyl C.sub.1 -C.sub.3 alkyl, phenyl, naphthyl, phenyl C.sub.1 -C.sub.4 alkyl, and naphthyl C.sub.1 -C.sub.4 alkyl, wherein any of the foregoing is optionally substituted with a C.sub.1 -C.sub.4 alkyl, amino, hydroxy, di(C.sub.1 -C.sub.4)alkylamino, C.sub.1 -C.sub.4 aminoalkyl, C.sub.1 -C.sub.4 alkoxy, carboxyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 carboxyalkyl, C.sub.2 -C.sub.5 acyloxy, phenyl, phenoxy, halogen, or phenyl (C.sub.1 -C.sub.4)dialkylamino, and R.sup.8 is hydrogen atom or C.sub.1 -C.sub.4 alkyl, or --R.sup.9 --OCOR.sup.10 where R.sup.9 is alkylene and R.sup.10 is selected from the group consisting of C.sub.1 -C.sub.12 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C.sub.1 -C.sub.8 alkyl, piperidyl C.sub.1 -C.sub.8 alkyl, piperidino C.sub.1 -C.sub.8 alkyl, morpholinyl C.sub.1 -C.sub.8 alkyl, morpholino C.sub.1 -C.sub.8 alkyl, piperazinyl C.sub.1 -C.sub.8 alkyl, pyrrolyl C.sub.1 -C.sub.8 alkyl, imidazolyl C.sub.1 -C.sub.8 alkyl, pyridyl C.sub.1 -C.sub.8 alkyl, wherein any of the foregoing is optionally substituted with a C.sub.1 -C.sub.4 alkyl, amino, hydroxy, C.sub.1 -C.sub.4 dialkylamino, C.sub.1 -C.sub.4 aminoalkyl, C.sub.1 -C.sub.4 alkoxy, carboxyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 carboxyalkyl, C.sub.2 -C.sub.5 acyloxy, phenyl, phenoxy, halogen, or phenyl di (C.sub.1 -C.sub.4)alkylamino, and the remaining three of R.sup.1, R.sup.2 R.sup.3, or R.sup.4 may be the same or different and each is independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl or a C.sub.1 -C.sub.4 alkoxy;R.sup.5 is selected from the group consisting of C.sub.1 -C.sub.12 alkyl, cyclo C.sub.3 -C.sub.6, alkyl, cyclo C.sub.3 -C.sub.6 alkyl C.sub.1 -C.sub.3 alkyl, phenyl, naphthyl, phenyl C.sub.1 -C.sub.4 alkyl, naphthyl C.sub.1 -C.sub.4 alkyl, pyrrolidinyl, piperidyl, piperidino, morpholinyl, morpholino, piperazinyl, pyrrolyl, imidazolyl, pyridyl, pyrrolidinyl C.sub.1 -C.sub.8 alkyl, piperidyl C.sub.1 -C.sub.8 alkyl, piperidino C.sub.1 -C.sub.8 alkyl, morpholinyl C.sub.1 -C.sub.8 alkyl, morpholino C.sub.1 -C.sub.8 alkyl, piperazinyl C.sub.1 -C.sub.8 alkyl, pyrrolyl C.sub.1 -C.sub.8 alkyl, imidazolyl C.sub.1 -C.sub.8 alkyl, pyridyl C.sub.1 -C.sub.8 alkyl, wherein any of the foregoing is optionally substituted with a C.sub.1 -C.sub.8 alkyl, amino, hydroxy, C.sub.1 -C.sub.4 dialkylamino, C.sub.1 -C.sub.4 aminoalkyl, C.sub.1 -C.sub.4 alkoxy, carboxyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4 carboxyalkyl, C.sub.2 -C.sub.5 acyloxy, phenyl, phenoxy, halogen, or phenyl di (C.sub.1 -C.sub.4)alkylamino, an alkenyl, an alkynyl, a dialkylaminoacyloxyalkyl, --R.sup.D SO.sub.3 D or a R.sup.E PO.sub.3 E where R.sup.D and R.sup.E are each alkylene and D and E are each alkali metal or hydrogen atom, and m is 1, ora pharmaceutically acceptable salt thereof, with the proviso that R.sup.5 is not ethyl when R.sup.1, R.sup.3, and R.sup.4 are hydrogen atom, R.sup.2 is (4-methylpentanoyl)amino, and m is 1.