US5049696A
Expired / Lapsed
US
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Antihypercholesterolemic compounds
Assignee: Merck and Co Inc
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Filing: 1989-06-14
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Granted: 1991-09-17
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Expires: 2009-06-14
Abstract
Abstract Novel 3-hydroxy-3-methylglutaryl-Coenzyme A(HMG-CoA) reductase inhibitors, which are useful as antihypercholesterolemic agents and are represented by the following general structural formulae (I) and (II) ##STR1## and pharmaceutically acceptable salts of the compound (II) in which Z is hydrogen are disclosed.
Inventors
- 👤 Ta J. Lee
- 👤 Clarence S. Rooney
- 👤 William F. Hoffman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 04:42
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
91 words
A compound represented by the following general structural formula (II): ##STR36## wherein: n is 2 to 7; R 1 is C 1-6 alkyl substituted with a group selected from halogen or hydroxy; C 1-6 alkylthio; phenylmethyl or 4-hydroxyphenylmethyl; A is ##STR37## b and d represent single bonds, or both b and d represent double bonds; Z is hydrogen, C 1-5 alkyl or C 1-5 alkyl substituted with a group selected from phenyl, dimethylamino or acetylamino; and pharmaceutically acceptable salts of the compounds of the formula (II) in which Z is hydrogen.
Claim 2
Dependent Claim
91 words
A compound represented by the following general structural formula (II): ##STR36## wherein: n is 2 to 7; R 1 is C 1-6 alkyl substituted with a group selected from halogen or hydroxy; C 1-6 alkylthio; phenylmethyl or 4-hydroxyphenylmethyl; A is ##STR37## b and d represent single bonds, or both b and d represent double bonds; Z is hydrogen, C 1-5 alkyl or C 1-5 alkyl substituted with a group selected from phenyl, dimethylamino or acetylamino; and pharmaceutically acceptable salts of the compounds of the formula (II) in which Z is hydrogen.
Claim 3
Dependent Claim
27 words
A compound of claim 1 wherein n is 2 to 5; and R 1 is C 1-6 alkyl; hydroxy-C 1-6 alkyl; C 1-6 alkylthio; phenylmethyl; or 4-hydroxyphenylmethyl.
Claim 4
Dependent Claim
9 words
A compound of claim 2 wherein n is 2.
Claim 5
Dependent Claim
9 words
A compound of claim 2 wherein n is 3.
Claim 6
Dependent Claim
9 words
A compound of claim 2 wherein n is 4.
Claim 7
Dependent Claim
9 words
A compound of claim 2 wherein n is 5.
Claim 8
Dependent Claim
22 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 9
Dependent Claim
27 words
A composition according to claim 7 wherein: n is 2 to 5;and R 1 is C 1-6 alkyl; hydroxy-C 1-6 alkyl; C 1-6 alkylthio; phenyl; or hydroxyphenyl.
Claim 10
Dependent Claim
44 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable nontoxic cationic polymer capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract and a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
28 words
A method of inhibiting cholesterol biosynthesis comprising the administration to a subject in need of such treatment a nontoxic therapeutically effective amount of a compound of claim 1.
Claim 12
Dependent Claim
27 words
A method of claim 10 wherein: n is 2 to 5; and R 1 is C 1-6 alkyl hydroxy-C 1-6 alkyl; C 1-6 alkylthio; phenyl; or hydroxyphenyl.
Claim 13
Dependent Claim
13 words
A compound of claim 3 which is 7-[1,2,6,7,8, 8a( R)-hexahydro-2(S), 6(R)-dimethyl-8(S)-(1-methylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 14
Dependent Claim
12 words
A compound of claim 4, which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S), 6(R)-dimethyl-8(S)-(1-methylcyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 15
Dependent Claim
11 words
A compound of claim 4 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S), 6(R)-dimethyl-8(S)-(1-methylthiocyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 16
Dependent Claim
10 words
A compound of claim 4 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-(3-hydroxypropyl)cyclobutanecarbonyloxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 17
Dependent Claim
10 words
A compound of claim 4 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-[(4-hydroxyphenyl) methyl]cyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 18
Dependent Claim
10 words
A compound of claim 4 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-(hydroxymethyl)cyclobutanecarbonyloxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 19
Dependent Claim
12 words
A compound of claim 4 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-8 1-(1-phenylmethyl) cyclobutanecarbonyloxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 20
Dependent Claim
10 words
A compound of claim 5 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclopentanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 21
Dependent Claim
10 words
A compound of claim 5 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylthiocycopentanecarbonyl)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 22
Dependent Claim
10 words
A compound of claim 6 which is 7-[1,2,6,7,8, 8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclohexanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 23
Dependent Claim
51 words
A composition according to claim 8 wherein the therapeutically active ingredient is selected from the group consisting of (1) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylthiocyclobutanecarbonyloxy)-1(S)naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-(3-hydroxypropyl)cyclobutanecarbonyloxy]1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (5) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-[(4-hydroxyphenyl)methyl]-cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (6) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[(1-hydroxymethyl)cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (7) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-(1-phenylmethyl)cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (8) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8 (S)-(1-methylcyclopentanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (9) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylthiocyclopentanecarbonyl)-3(R), 5(R)-dihydroxyheptanoic acid; (10) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclocyclohexanecarbonyloxy)-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 24
Dependent Claim
50 words
A method of claim 11 wherein the therapeutically active ingredient is selected from the group consisting of: (1) 6(R)-[2-[8(S)-[(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylthiocyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-(3-hydroxypropyl)cyclobutanecarbonyloxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (5) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-[(4-hydroxyphenyl)methyl]cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (6) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[(1-hydroxymethyl)cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (7) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[1-(1-phenylmethyl)cyclobutanecarbonyloxy]-3(R),5(R)-dihydroxyheptanoic acid; (8) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclopentanecarbonyloxy]-3(R), 5(R)-dihydroxyheptanoic acid; (9) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylthiocyclopentanecarbonyl)-3(R), 5(R)-dihydroxyheptanoic acid; (10) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-methylcyclocyclohexanecarbonyloxy)-3(R), 5(R)-dihydroxyheptanoic acid.
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