Biarylimidazoles as inhibitors of microsomal prostaglandin E2 synthase-1

Bioorg Med Chem Lett. 2010 Dec 1;20(23):6978-82. doi: 10.1016/j.bmcl.2010.09.129. Epub 2010 Oct 19.

Abstract

Microsomal prostaglandin E(2) synthase (mPGES-1) represents a potential target for novel analgesic and anti-inflammatory agents. High-throughput screening identified several leads of mPGES-1 inhibitors which were further optimized for potency and selectivity. A series of inhibitors bearing a biaryl imidazole scaffold exhibits excellent inhibition of PGE(2) production in enzymatic and cell-based assays. The synthesis of these molecules and their activities will be discussed.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • High-Throughput Screening Assays
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Mice
  • Microsomes / enzymology*
  • Prostaglandin-E Synthases

Substances

  • Anti-Inflammatory Agents
  • Imidazoles
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
  • Dinoprostone