Synthesis and biological activity of new HMG-CoA reductase inhibitors. 2. Derivatives of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)-enoic (-heptanoic) acids

J Med Chem. 1990 Jan;33(1):61-70. doi: 10.1021/jm00163a011.

Abstract

A series of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)- enoates (-heptanoates) 1 and 2 have been prepared and tested for inhibiti 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The most potent compounds exceeded mevinolin's activity in vitro and in vivo.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticholesteremic Agents
  • Carcinoma, Hepatocellular / metabolism
  • Chemical Phenomena
  • Chemistry
  • Cholesterol / biosynthesis*
  • Cholesterol / blood
  • Dogs
  • Heptanoic Acids / chemical synthesis
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Neoplasms / metabolism
  • Lovastatin / pharmacology
  • Male
  • Molecular Structure
  • Pyrroles / chemical synthesis
  • Pyrroles / pharmacology*
  • Rabbits
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Cholesterol
  • Lovastatin