Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
AssigneeWarner-Lambert Company
InventorBruce D. Roth
Life of this patent
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Abstract
Certain trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-ones and the corresponding ring-opened acids derived therefrom which are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase and are thus useful hypolipidemic or hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions are also disclosed.
Claims9
A compound of structural formula I ##STR17## wherein X is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 CH.sub.2 --, or --CH.sub.2 CH(CH.sub.3)--;
- R.sub.1 is
- 1-naphthyl;
- 2-naphthyl;
- cyclohexyl;
- norbornenyl;
- phenyl;
- phenyl substituted with
- fluorine,
- chlorine,
- bromine,
- hydroxyl,
- trifluoromethyl,
- alkyl of from one to four carbon atoms,
- alkoxy of from one to four carbon atoms, or
- alkanoyloxy of from two to eight carbon atoms;
- either of R.sub.2 or R.sub.3 is --CONR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are independently
- hydrogen;
- alkyl of from one to six carbon atoms;
- phenyl;
- phenyl substituted with
- fluorine,
- chlorine,
- bromine,
- cyano,
- trifluoromethyl, or
- carboalkoxy of from three to eight carbon atoms;
- and the other of R.sub.2 or R.sub.3 is
- hydrogen;
- alkyl of from one to six carbon atoms;
- cyclopropyl;
- cyclobutyl;
- cyclopentyl;
- cyclohexyl;
- phenyl;
- or
- phenyl substituted with
- fluorine,
- chlorine,
- bromine,
- hydroxyl,
- trifluoromethyl,
- alkyl of from one to four carbon atoms,
- alkoxy of from one to four carbon atoms, or
- alkanoyloxy of from two to eight carbon atoms;
- R.sub.4 is
- alkyl of from one to six carbon atoms;
- cyclopropyl;
- cyclobutyl;
- cyclopentyl;
- cyclohexyl;
- or
- trifluoromethyl;
- or a hydroxy acid or pharmaceutically acceptable salts thereof, corresponding to the opened lactone ring of the compounds of structural formula I above.
Dependencies are inferred from the claim text.