US4937263A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Antihypercholesterolemic compounds
Assignee: Merck and Co Inc
•
Filing: 1989-07-17
•
Granted: 1990-06-26
•
Expires: 2009-07-17
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 compounds (II) in which Z is hydrogen are disclosed.
Inventors
- 👤 William F. Hoffman
- 👤 Ta J. Lee
- 👤 Robert L. Smith
- 👤 Clarence S. Rooney
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:20
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
132 words
A compound represented by the following general structural formula (II'): ##STR48## wherein: n is 0 to 2; R 1 is C 1-3 alkyl; R 2 is hydrogen or C 1-3 alkyl; each of the R 3 s and R 4 s are independently selected from hydrogen or C 1-3 alkyl; "X and Y independently are hydrogen, trifluoromethyl, hydroxy, C 1-3 alkyl thiomethyl, hydroxymethyl, or aminomethyl, provided that both X and Y are not hydrogen;" A is ##STR49## b and d represent single bonds, or both b and d represent double bonds; and Z is hydrogen, C 1-5 alkyl or C 1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; or a pharmaceutically acceptable salt of the compound of the formula (II') in which Z is hydrogen.
Claim 2
Dependent Claim
132 words
A compound represented by the following general structural formula (II'): ##STR48## wherein: n is 0 to 2; R 1 is C 1-3 alkyl; R 2 is hydrogen or C 1-3 alkyl; each of the R 3 s and R 4 s are independently selected from hydrogen or C 1-3 alkyl; "X and Y independently are hydrogen, trifluoromethyl, hydroxy, C 1-3 alkyl thiomethyl, hydroxymethyl, or aminomethyl, provided that both X and Y are not hydrogen;" A is ##STR49## b and d represent single bonds, or both b and d represent double bonds; and Z is hydrogen, C 1-5 alkyl or C 1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; or a pharmaceutically acceptable salt of the compound of the formula (II') in which Z is hydrogen.
Claim 3
Dependent Claim
29 words
A compound according to claim 1 wherein R 1 is methyl; "X and Y independently are hydrogen, trifluoromethyl or hydroxy, provided that both X and Y are not hydrogen."
Claim 4
Dependent Claim
10 words
A compound according to claim 2 wherein n is 0.
Claim 5
Dependent Claim
11 words
A compound according to claim 3 wherein R 2 is methyl.
Claim 6
Dependent Claim
16 words
A compound according to claim 4 wherein X is hydroxy; and Y is hydrogen or hydroxy.
Claim 7
Dependent Claim
10 words
A compound according to claim 5 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(α,α-dimethyl-4'-hydroxyphenylacetyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 8
Dependent Claim
11 words
A compound according to claim 5 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(α,α-dimethyl-3'-hydroxyphenylacetyloxy)1(S)-naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 9
Dependent Claim
11 words
A compound according to claim 5 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(α,α-dimethyl-4'-hydroxymethylphenylacetyloxy)1(S)-naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 10
Dependent Claim
10 words
A compound according to claim 2 wherein n is 1.
Claim 11
Dependent Claim
25 words
A compound according to claim 9 wherein R 2 is methyl; R 3 and R 4 are hydrogen; and b and d represent double bonds.
Claim 12
Dependent Claim
16 words
A compound according to claim 10 wherein X is hydroxy; and Y is hydrogen or hydroxy,
Claim 13
Dependent Claim
11 words
A compound according to claim 11 which is 7-[1,2,6,7,8,8a,(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[(α,α-dimethyl-3-(4'-hydroxyphenyl)-propionyloxy]-1(S)-naphthyl]-3-(R), 5(R)-dihydroxyheptanoic acid.
Claim 14
Dependent Claim
10 words
A compound according to claim 11 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[(α,α-dimethyl-3-(3',5'-dihydroxyphenyl)-propionyl-oxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 15
Dependent Claim
10 words
A compound according to claim 2 wherein n is 2.
Claim 16
Dependent Claim
22 words
A hypocholesterolemic, hypolipdemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
29 words
A composition according to claim 15 wherein R 1 is methyl; "X and Y independently are hydrogen, trifluoromethyl or hydroxy, provided that both X and Y are not hydrogen."
Claim 18
Dependent Claim
18 words
A composition according to claim 16 wherein R 2 is methyl; and b and d are double bonds.
Claim 19
Dependent Claim
16 words
A composition according to claim 17 wherein X is hydroxy; and Y is hydrogen or hydroxy,
Claim 20
Dependent Claim
30 words
A composition according to claim 18 wherein the therapeutically active ingredient is selected from the group consisting of (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(α,α-dimethyl-4'-hydroxyphenylacetyloxy)-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)-(α,α-dimethyl-3'-hydroxyphenylacetyloxy)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)-(α,α-dimethyl-4'-hydroxymethylphenylacetyloxy)-1(S)naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid;
Claim 21
Dependent Claim
25 words
A compound according to claim 18 wherein the therapeutically active ingredient is selected from the group consisting of (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(α,α-dimethyl-3-(4'-hydroxyphenyl)-propionyloxy)-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)-(α,α-dimethyl-3-(3',5'-dihydroxyphenyl)propionyloxy)-1(S)naphthyl]-3(R), 5(R)-dihydroxyheptanoic acid.
Claim 22
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 23
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.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-06-25 | 1993-12-25 | 1994-06-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-06-25 | 1997-12-25 | 1998-06-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-06-25 | 2001-12-25 | 2002-06-26 | $7700.00 | Window Closed / Lapsed |