Synthesis of 1,5-diarylhaloimidazole analogs and their inhibitory activities against PGE₂ production from LPS-treated RAW 264.7 cells

Bioorg Med Chem. 2012 Nov 1;20(21):6256-9. doi: 10.1016/j.bmc.2012.09.014. Epub 2012 Sep 16.

Abstract

A number of 1,5-diarylimidazole analogs were synthesized and evaluated their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin E(2) production. Reactions of 1,5-diarylimidazoles with halogenating reagents (NCS, NBS, NIS) afforded halogenated analogs. Among the analogs tested, compounds Ib, IIa, IIb and IIe exhibited significantly improved inhibitory activities against COX-2-mediated PGE(2) production from LPS-induced RAW 264.7 cells compared to those of the parent 1,5-diarylimidazoles. Especially, the analogs Ib (IC(50)=0.55 μM) and IIa (IC(50)=0.58 μM) showed best results. Halogenation on the 1,5-diarylimidazole ring enhanced inhibitory activities against COX-2 catalyzed PGE(2) production, however, inhibitory activities were significantly varied by position(s) and species of the substituted halogen(s).

MeSH terms

  • Animals
  • Cells, Cultured
  • Dinoprostone / analysis
  • Dinoprostone / biosynthesis*
  • Dose-Response Relationship, Drug
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Imidazoles
  • Lipopolysaccharides
  • Dinoprostone