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US 5,686,433 AGranted
Quinoline and pyridine anchors for HMG-CoA reductase inhibitors
AssigneeE.R. Squibb & Sons, Inc.
InventorJeffrey Adam Robl
Life of this patent
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Abstract
Compounds which are useful as inhibitors of cholesterol biosynthesis and thus as hypocholesterolemic agents are provided which have a quinoline or a pyridine anchor attached by means of a linker to a binding domain sidechain, which compounds inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.
Claims14
A compound of the formula ##STR56## or a pharmaceutically acceptable salt thereof wherein:
- Am is ##STR57## X is --(CH.sub.2).sub.a --, --CH.dbd.CH--, --C.tbd.C-- or --CH.sub.2 O--;
- R.sup.1 and R.sup.2 are the same or different and are each independently selected from
- (i) hydrogen,
- (ii) alkyl,
- (iii) aryl,
- (iv) cycloalkyl,
- (v) aralkyl,
- (vi) aralkoxy,
- (vii) alkenyl, and
- (viii) cycloalkenyl;
- R.sup.3 and R.sup.4 taken together is ##STR58## q is 0, 1, 2 or 3 and r is 0, 1, 2 or 3, at least one of q and r being other than zero;
- R.sup.5 and R.sup.7 are each independently selected form hydrogen, lower alkyl, alkali metal salt ion and alkaline earth metal salt ion;
- R.sup.6 is hydrogen or lower alkyl;
- R.sup.8 is hydrogen or lower alkyl in the free acid form or in the form of a physiologically acceptable and hydrolyzable ester or .delta.-lactone thereof, or an alkali metal salt ion or alkaline earth metal salt ion;
- n is 0 or 1;
- and
- a is 1, 2 or 3, and wherein "aryl" by itself or as part of another group is a monocyclic or bicyclic aromatic group containing 6 to 10 carbons in the ring portion;
- "alkyl" or "lower alkyl" by itself or as part of another group contains 1 to 12 carbons;
- "cycloalkyl" by itself or as part of another group contains 3 to 12 carbons;
- "cycloalkenyl" by itself or as part of another group contains 3 to 12 carbons.
17 more elements
The compound as defined in claim 15 wherein R.sup.1 or R.sup.2 is fluorophenyl or isopropyl.
A compound of the formula ##STR61## or a pharmaceutically acceptable salt thereof wherein:
- Am is ##STR62## X is --(CH.sub.2).sub.a --, --CH.dbd.CH--, --C.tbd.C-- or --CH.sub.2 O--;
- R.sup.1 and R.sup.2 are the same or different and are each independently selected from
- (i) hydrogen,
- (ii) alkyl,
- (iii) aryl,
- (iv) cycloalkyl and
- (v) alkenyl,
- R.sup.3 and R.sup.4 taken together is ##STR63## q is 0, 1, 2 or 3 and r is 0, 1, 2 or 3, at least one of q and r being other than zero;
- R.sup.5 and R.sup.7 are each independently selected form hydrogen, lower alkyl, alkali metal salt ion and alkaline earth metal salt ion;
- R.sup.6 is hydrogen or lower alkyl;
- R.sup.8 is hydrogen or lower alkyl in the free acid form or in the form of a physiologically acceptable and hydrolyzable ester or .delta.-lactone thereof, or an alkali metal salt ion or alkaline earth metal salt ion;
- n is 0 or 1;
- and
- a is 1, 2 or 3 and wherein "aryl" by itself or as part of another group is a monocyclic or bicyclic aromatic group containing 6 to 10 carbons in the ring portion;
- "alkyl" or "lower alkyl" by itself or as part of another group contains 1 to 12 carbons;
- "cycloalkyl" by itself or as part of another group contains 3 to 12 carbons;
- "cycloalkenyl" by itself or as part of another group contains 3 to 12 carbons.
14 more elements
Dependencies are inferred from the claim text.