Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation

W Shen; D S Garvey; J Cohen; H Stein; S H Rosenberg

doi:10.1016/s0960-894x(98)00143-7

Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation

Bioorg Med Chem Lett. 1998 Apr 21;8(8):891-6. doi: 10.1016/s0960-894x(98)00143-7.

Authors

W Shen¹, D S Garvey, J Cohen, H Stein, S H Rosenberg

Affiliation

¹ Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA.

PMID: 9871507
DOI: 10.1016/s0960-894x(98)00143-7

Abstract

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.

MeSH terms

Animals
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry
Cyclopentanes / pharmacology
Dicarboxylic Acids / chemical synthesis*
Dicarboxylic Acids / chemistry
Dicarboxylic Acids / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
Indicators and Reagents
Isomerism
Microsomes, Liver / enzymology
Models, Molecular
Molecular Conformation
Molecular Structure
Rats
Structure-Activity Relationship
Tricarboxylic Acids / chemical synthesis*
Tricarboxylic Acids / chemistry
Tricarboxylic Acids / pharmacology

Substances

Cyclopentanes
Dicarboxylic Acids
Enzyme Inhibitors
Indicators and Reagents
Tricarboxylic Acids
Farnesyl-Diphosphate Farnesyltransferase