Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4531-7. doi: 10.1016/j.bmcl.2007.05.097. Epub 2007 Jun 6.

Abstract

Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

MeSH terms

  • Animals
  • Cholesterol / biosynthesis
  • Drug Design
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemical synthesis*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hyperlipidemias / drug therapy
  • Mice
  • Molecular Biology
  • Molecular Structure
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Cholesterol

Associated data

  • PDB/2Q6B
  • PDB/2Q6C