Three-dimensional quantitative structure (3-D QSAR) activity relationship studies on imidazolyl and N-pyrrolyl heptenoates as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitors by comparative molecular similarity indices analysis (CoMSIA)

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1027-32. doi: 10.1016/j.bmcl.2004.12.042.

Abstract

A comparative molecular similarity indices analysis (CoMSIA) of a set of 29 imidazolyl and N-pyrrolyl heptenoates have been performed to find out the structural requirements for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory activity. The HMG like side chain, a common moiety of statins, was used to align the molecules. The results guide to design new chemical entities with high potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Heptanoic Acids / chemistry*
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / chemistry*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Imidazoles
  • Inhibitory Concentration 50
  • Models, Molecular
  • Protein Conformation
  • Pyrroles
  • Quantitative Structure-Activity Relationship*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Imidazoles
  • Pyrroles
  • Hydroxymethylglutaryl CoA Reductases