US4647576A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis
Assignee: Warner Lambert Co LLC
•
Filing: 1984-12-10
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Granted: 1987-03-03
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Expires: 2004-12-10
Abstract
Abstract 6-[2-(Substituted-pyrrol-1-yl)alkyl]pyran-2-ones and the corresponding ring-opened hydroxy-acids derived therefrom are potent inhibitors of the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA reductase), and are thus useful hypolipidemic and hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of treatment employing such pharmaceutical compositions are also disclosed.
Inventors
- 👤 Milton L. Hoefle
- 👤 Bruce D. Roth
- 👤 Charlotte D. Stratton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 12:53
CPC Classifications
C; C07; C07D; C07D405/00; C07D405/02; C07D405/06; C07D407/00; C07D407/02; C07D407/06; C07D487/00; C07D487/02; C07D487/04; C07D491/00; C07D491/02; C07D491/04
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
130 words
A compound having the structural formula ##STR27## wherein X is --CH 2 --, --CH 2 CH 2 --, or --CH(CH 3 )CH 2 --; R 1 is 1-naphthyl, 2-naphthyl, cyclohexyl, norbornenyl, phenyl, phenyl substituted by fluorine, chlorine, hydroxy, trifluoromethyl, alkyl of from one to four carbon atoms, alkoxy of from one to four carbon atoms, alkanoyloxy of from two to eight carbon atoms, 2-, 3-, or 4-pyridinyl, 2-, 3-, or 4-pyridinyl-N-oxide, R 2 and R 3 are independently hydrogen, chlorine, bromine, cyano, trifluoromethyl, phenyl, alkyl of from one to four carbon atoms, carboalkoxy of from two to eight carbon atoms, R 4 is alkyl of from one to four carbon atoms, cyclopropyl, cyclobutyl, or trifluoromethyl; or a corresponding lactone ring-opened dihydroxy acid derived therefrom, or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
130 words
A compound having the structural formula ##STR27## wherein X is --CH 2 --, --CH 2 CH 2 --, or --CH(CH 3 )CH 2 --; R 1 is 1-naphthyl, 2-naphthyl, cyclohexyl, norbornenyl, phenyl, phenyl substituted by fluorine, chlorine, hydroxy, trifluoromethyl, alkyl of from one to four carbon atoms, alkoxy of from one to four carbon atoms, alkanoyloxy of from two to eight carbon atoms, 2-, 3-, or 4-pyridinyl, 2-, 3-, or 4-pyridinyl-N-oxide, R 2 and R 3 are independently hydrogen, chlorine, bromine, cyano, trifluoromethyl, phenyl, alkyl of from one to four carbon atoms, carboalkoxy of from two to eight carbon atoms, R 4 is alkyl of from one to four carbon atoms, cyclopropyl, cyclobutyl, or trifluoromethyl; or a corresponding lactone ring-opened dihydroxy acid derived therefrom, or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
43 words
A compound in accordance with claim 1 wherein X is --CH 2 CH 2 --; R 1 is as defined in claim 1; R 2 and R 3 are independently hydrogen, chlorine, or bromine; and R 4 is as defined in claim 1.
Claim 4
Dependent Claim
82 words
A compound in accordance with claim 1 wherein X is --CH 2 CH 2 --; R 1 is phenyl, phenyl substituted by fluorine, chlorine, hydroxy, trifluoromethyl, alkyl of from one to four carbon atoms, alkoxy of from one to four carbon atoms, alkanoyloxy of from two to eight carbon atoms, 2-, 3-, or 4-pyridinyl, 2-, 3-, or 4-pyridinyl-N-oxide, R 2 and R 3 are independently hydrogen, chlorine, bromine; and R 4 is alkyl of from one to four carbon atoms, or trifluoromethyl.
Claim 5
Dependent Claim
61 words
A compound in accordance with claim 1 wherein X is --CH 2 CH 2 --; R 1 is phenyl, or phenyl substituted by fluorine, chlorine, hydroxy, trifluoromethyl, alkoxy of from one to four carbon atoms, alkanoyloxy of from two to eight carbon atoms; R 2 and R 3 are independently hydrogen, chlorine, or bromine; and R 4 is isopropyl or trifluoromethyl.
Claim 6
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[3,4-dichloro-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 7
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[3,4-dibromo-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 8
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrrol-1-yl)ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 9
Dependent Claim
12 words
A compound in accordance with claim 1 having the name trans-dimethyl 2-(4-fluorophenyl)-5-(1-methylethyl)-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3,4-dicarboxylate.
Claim 10
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-(4-fluorophenyl-5-methyl-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 11
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-(4-fluorophenyl-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 12
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-cyclopropyl-5-(4-fluorophenyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 13
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-(1,1-dimethylethyl)-5-(4-fluorophenyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 14
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-tetrahydro-4-hydroxy-6-[2-[2-(2-methoxyphenyl)-5-methyl-1H-pyrrol-1-yl]ethyl]-2H-2-one.
Claim 15
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-tetrahydro-4-hydroxy-6-[2-[2-(2-methoxyphenyl)-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]-2H-pyran-2-one.
Claim 16
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-tetrahydro-4-hydroxy-6-[2-[2-methyl-5-(1-naphthalenyl)-1H-pyrrol-1-yl]ethyl]-2H-pyran-2-one.
Claim 17
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-(2-bicyclo[2.2.1]hep-5-en-2-yl-5-methyl-1H-pyrrol-1-yl)ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 18
Dependent Claim
11 words
A compound in accordance with claim 1 having the name trans-6-[2-[2-(4-fluorophenyl)-5-(1-methylphenyl)-1H-pyrrol-1-yl]propyl]tetrahydro-4-hydroxy-2H-pyran-2-one.
Claim 19
Dependent Claim
28 words
A pharmaceutical composition, useful as a hypocholesterolemic agent, comprising a hypocholesterolemic effective amount of a compound in accordance with claim 1 in combination with a pharmaceutically acceptable carrier.
Claim 20
Dependent Claim
25 words
A method of treating inhibiting cholesterol biosynthesis in a patient in need of such treatment by administering a pharmaceutical composition in accordance with claim 18.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1990-03-02 | 1990-09-01 | 1991-03-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-03-02 | 1994-09-01 | 1995-03-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-03-02 | 1998-09-01 | 1999-03-03 | $7700.00 | Window Closed / Lapsed |