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.

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