Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4538-44. doi: 10.1016/j.bmcl.2007.05.096. Epub 2007 Jun 6.

Abstract

This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

MeSH terms

  • Animals
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Drug Design
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hyperlipidemias / drug therapy
  • Liver / drug effects
  • Models, Molecular
  • Molecular Structure
  • Pyrimidines
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology*
  • Rosuvastatin Calcium
  • Structure-Activity Relationship
  • Sulfonamides

Substances

  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Rosuvastatin Calcium

Associated data

  • PDB/2Q1L