US4900754A
Expired / Lapsed
US
⏱️ 0.0 years remaining
HMG-COA reductase inhibitors
Assignee: Aventis Pharmaceuticals Inc
•
Filing: 1989-03-27
•
Granted: 1990-02-13
•
Expires: 2009-03-27
Abstract
Abstract Disclosed are novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors useful as antihypercholesterolemic agents represented by the formula ##STR1## and the corresponding ring-opened hydroxy acids derived therefrom and pharmaceutically acceptable salts thereof. Pharmaceutical compositions containing said compounds and method of inhibiting the biosynthesis of cholesterol therewith are also disclosed.
Inventors
- 👤 John R. Regan
- 👤 Kent W. Neuenschwander
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 17:13
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C07C; C07C59/00; C07C59/40; C07C59/42; C07C59/54; C07C59/56; C07C59/58; C07C59/64
Claims Analysis
Total Claims: 50
Claim 1
Independent Claim
70 words
A compound of the formula ##STR10## wherein Y is: --CHR--, --CHRCHR--, --CHRCHRCHR--, or --RC═CR--; X, X 1 and X 2 are independently: R, NO 2 , NH(CO)R, N(R) 2 , S(O) m R, F, Cl, or Br; R 1 is: OR; R 2 is: R; R 3 and R 4 are independently: H or lower alkyl; R is: H or lower alkyl; n is: - 2; and m is: 0-2i
Claim 2
Dependent Claim
70 words
A compound of the formula ##STR10## wherein Y is: --CHR--, --CHRCHR--, --CHRCHRCHR--, or --RC═CR--; X, X 1 and X 2 are independently: R, NO 2 , NH(CO)R, N(R) 2 , S(O) m R, F, Cl, or Br; R 1 is: OR; R 2 is: R; R 3 and R 4 are independently: H or lower alkyl; R is: H or lower alkyl; n is: - 2; and m is: 0-2i
Claim 3
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3,5-dimethylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 4
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3,5-dimethylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 5
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluorophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy--3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 6
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluorophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy--3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 7
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 8
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 9
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 10
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 11
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-butoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 12
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-butoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 13
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-nitrophenyl)-4-hydroxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 14
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-nitrophenyl)-4-hydroxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 15
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-nitro-3-methylphenyl)-4-methoxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 16
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-nitro-3-methylphenyl)-4-methoxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 17
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-dimethylaminophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 18
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-dimethylaminophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 19
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-ethylthio-3-fluorophenyl)-4-propoxy-6,6-dimethylcyclohex-2-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 20
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-ethylthio-3-fluorophenyl)-4-propoxy-6,6-dimethylcyclohex-2-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 21
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-butylsulfonyl-3-methylphenyl)-4-hydroxy-7,7-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 22
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-butylsulfonyl-3-methylphenyl)-4-hydroxy-7,7-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 23
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(3-acetamidophenyl)-4-methoxy-4,7,7-triethylcyclohept-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 24
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(3-acetamidophenyl)-4-methoxy-4,7,7-triethylcyclohept-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 25
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-propionamidophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 26
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-propionamidophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 27
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-chloro-3-ethylphenyl)-4-(1,1-dimethylethoxy)-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 28
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-chloro-3-ethylphenyl)-4-(1,1-dimethylethoxy)-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 29
Dependent Claim
1 words
Trans-6-[2-[2-(4-fluorophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 30
Dependent Claim
1 words
Trans-6-[2-[2-(4-fluorophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 31
Dependent Claim
1 words
Trans-6-[2-[2-(5-dimethylamino-4-fluoro-3-methylphenyl)-4-ethoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 32
Dependent Claim
1 words
Trans-6-[2-[2-(5-dimethylamino-4-fluoro-3-methylphenyl)-4-ethoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 33
Dependent Claim
1 words
Trans-6-[2-[2-(4-fluoro-3-methylphenyl)-4-hexyloxy-6-ethyl-6-phenylcyclohex-1-en-1-yl]ethyl]4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 34
Dependent Claim
1 words
Trans-6-[2-[2-(4-fluoro-3-methylphenyl)-4-hexyloxy-6-ethyl-6-phenylcyclohex-1-en-1-yl]ethyl]4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 35
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(5-chloro-4-acetamido-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 36
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(5-chloro-4-acetamido-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 37
Dependent Claim
1 words
Trans-6-[2-[2-(4-dipropylamino-3-propylphenyl)-4-propoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 38
Dependent Claim
1 words
Trans-6-[2-[2-(4-dipropylamino-3-propylphenyl)-4-propoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 39
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluorophenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 40
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluorophenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 41
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 42
Dependent Claim
1 words
Trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 43
Dependent Claim
21 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 44
Dependent Claim
23 words
The hypocholesterolemic, hypolipidemic pharmaceutical composition of claim 22 wherein said compound is selected from the group consisting of: trans-(E)-6-[2-[2-(4-fluoro-3,5-dimethylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-fluorophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 45
Dependent Claim
23 words
The hypocholesterolemic hypolipidemic pharmaceutical composition of claim 22 wherein said compound is selected from the group consisting of: trans-(E)-6-[2-[2-(4-fluoro-3-methylphenyl)-4-butoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-nitrophenyl)-4-hydroxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-nitro-3-methylphenyl)-4-methoxy-5,5-dimethylcyclopent-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-(E)-6-[2-[2-(4-dimethylaminophenyl)-4-hydroxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 46
Dependent Claim
23 words
The hypocholesterolemic, hypolipidemic pharmaceutical composition of claim 22 wherein said compound is selected from the group consisting of: trans-(E)-6-[2-[2-(4-ethylthio-3-fluorophenyl)-4-propoxy-6,6-dimethylcyclohex-2-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-butylsulfonyl-3-methylphenyl)-4-hydroxy-7,7-dimethylcyclohept-1-en-1-yl]ethenyl-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(3-acetamidophenyl)-4-methoxy-4,7,7-triethylcyclohept-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-(E)-6-[2-[2-(4-fluoro-3-propionamidophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 47
Dependent Claim
22 words
The hypocholesterolemic hypolipidemic pharmaceutical composition of claim 2 wherein said compound is selected from the group consisting of: trans-(E)-6-[2-[2-(4-chloro-3-ethylphenyl)-4-(1,1-dimethylethoxy)-6,6-dimetyhylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one trans-6-[2-[2-(4-fluorophenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-6-[2-[2-(5-dimethylamino-4-fluoro-3-methylphenyl)-4-ethoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 48
Dependent Claim
21 words
The hypocholesterolemic, hypolipidemic pharmaceutical composition of claim 22 wherein said compound is selected from the group consisting of: trans-6-[2-[2-(4-fluoro-3-methylphenyl)-4-hexyloxy-6-ethyl-6-methylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-(E)-6-[2-[2-(5-chloro-4-acetamido-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 49
Dependent Claim
22 words
The hypocholesterolemic, hypolipidemic pharmaceutical composition of claim 22 wherein said compound is selected from the group consisting of: trans-6-[2-[2-(4-dipropylamino-3-propylphenyl)-4-propoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; trans-(E)-6-[2-[2-(4-fluorophenyl)-4-methoxy-4,6,6-trimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and trans-(E)-6-[2-[2-[2-(4-fluoro-3-methylphenyl)-4-hydroxy-6,6-dimethylcyclohex-1-en-1-yl]ethenyl]-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Claim 50
Dependent Claim
23 words
A method of inhibiting cholesterol biosynthesis in a patient in need of such treatment comprising administering a pharmaceutical composition defined in claim 22.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-02-12 | 1993-08-14 | 1994-02-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-02-12 | 1997-08-14 | 1998-02-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-02-12 | 2001-08-14 | 2002-02-13 | $7700.00 | Window Closed / Lapsed |