Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation.
Based on earlier lead squalene synthase inhibitor A-87049 (3) and zaragozic acids, a series of cyclopentanedi- and tricarboxylic acids were synthesized and evaluated against the enzyme. Some exhibited good potency and SAR revealed the importance of conformation and substitution pattern of these synthetic inhibitors.
Shen
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Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Garvey
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DS
Cohen
J
J
Stein
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H
Rosenberg
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SH
D000818:Animals; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D007536:Isomerism; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014233:Tricarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D003517:Cyclopentanes; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D014233:Tricarboxylic Acids; D013186:Farnesyl-Diphosphate Farnesyltransferase