1-(1,3-Benzodioxol-5-ylmethyl)-3-[4-(1H-imidazol-1-yl)phenoxy]-piperidine analogs as potent and selective inhibitors of nitric oxide formation

Bioorg Med Chem Lett. 2007 May 1;17(9):2499-504. doi: 10.1016/j.bmcl.2007.02.053. Epub 2007 Feb 27.

Abstract

A new series of 1-(1,3-benzodioxol-5-ylmethyl)-3-[4-(1H-Imidazol-1-yl)phenoxy]-piperidine analogs were designed and identified as potent and selective inhibitors of NO formation based both on the crystal structure of a murine iNOS Delta114 monomer domain/ inhibitor complex and inhibition of the NO formation in human A172 cell assays. Compound 12S showed high potency and high iNOS selectivity versus nNOS and eNOS.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods*
  • Dimerization
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Inhibitory Concentration 50
  • Mice
  • Models, Chemical
  • Molecular Conformation
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology

Substances

  • 1-(1,3-benzodioxol-5-ylmethyl)-3-(4-(1H-imidazol-1-yl)phenoxy)-piperidine
  • Enzyme Inhibitors
  • Imidazoles
  • Piperidines
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III