Antihypercholesterolemic compounds
AssigneeMerck & Co., Inc.
InventorsWilliam F. Hoffman, Robert L. Smith, Alvin K. Willard
Life of this patent
Estimating the term…
Abstract
6(R)-[2-(8'-acyloxy-2'-methyl-6'-methyl (or hydrogen)-polyhydronaphthyl-1')-ethyl]-4 (R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-ones are prepared by acylation of the corresponding 8'-hydroxy compounds. The products are strong inhibitors of the biosynthesis of cholesterol.
Claims18
A compound of the formula:
- ##STR68## wherein R' is H or CH.sub.3 ;
- R is
- (1) 1,1-dimethylpropyl,
- (2) C.sub.3-10 cycloalkyl,
- (3) C.sub.2-10 alkenyl,
- (4) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (5) phenyl,
- (6) halophenyl,
- (7) phenyl-C.sub.1-3 alkyl,
- (8) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone;
- or the corresponding dihydroxy acid of the formula:
- ##STR69## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C.sub.1-4 alkyl ester of said acid.
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula:
- ##STR70## in which R' is H or CH.sub.3 ;
- R is
- (1) 1,1-dimethylpropyl,
- (2) C.sub.3-10 cycloalkyl,
- (3) C.sub.2-10 alkenyl,
- (4) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (5) phenyl,
- (6) halophenyl,
- (7) phenyl-C.sub.1-3 alkyl,
- (8) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone;
- or
- the corresponding dihydroxy acid of the formula:
- ##STR71## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C.sub.1-4 alkyl ester of said acid.
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula:
- ##STR72## in which R' is H or CH.sub.3 ;
- R is
- (1) 1,1-dimethylpropyl,
- (2) C.sub.3-10 cycloalkyl,
- (3) C.sub.2-10 alkenyl,
- (4) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (5) phenyl,
- (6) halophenyl,
- (7) phenyl-C.sub.1-3 alkyl,
- (8) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone;
- or
- the corresponding dihydroxy acid of the formula:
- ##STR73## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C.sub.1-4 alkyl ester of said acid.
A compound of the formula:
- ##STR74## wherein R' is H or CH.sub.3 ;
- R is
- (1) C.sub.3-10 cycloalkyl,
- (2) C.sub.2-10 alkenyl,
- (3) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (4) phenyl,
- (5) halophenyl,
- (6) phenyl-C.sub.1-3 alkyl
- (7) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone or the corresponding dihydroxy acid of the formula:
- ##STR75## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C.sub.1-4 alkyl ester of said acid.
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula:
- ##STR76## in which R' is H or CH.sub.3 ;
- R is
- (1) C.sub.3-10 cycloalkyl,
- (2) C.sub.2-10 alkenyl,
- (3) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (4) phenyl,
- (5) halophenyl,
- (6) phenyl-C.sub.1-3 alkyl,
- (7) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone;
- or
- the corresponding dihydroxy acid of the formula:
- ##STR77## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C.sub.1-4 alkyl ester of said acid.
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula:
- ##STR78## in which R' is H or CH.sub.3 ;
- R is
- (1) C.sub.3-10 cycloalkyl,
- (2) C.sub.2-10 alkenyl,
- (3) C.sub.1-10 CF.sub.3 -substituted alkyl,
- (4) phenyl,
- (5) halophenyl,
- (6) phenyl-C.sub.1-3 alkyl,
- (7) substituted phenyl-C.sub.1-3 alkyl in which the substituent is halo, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone;
- or
- the corresponding dihydroxy acid of the formula:
- ##STR79## or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted C.sub.1-4 alkyl ester of said acid.
Dependencies are inferred from the claim text.