2-Phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives: new potent inhibitors of fMLP-induced neutrophil chemotaxis

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3696-701. doi: 10.1016/j.bmcl.2007.04.036. Epub 2007 Apr 19.

Abstract

It is well known that both acute and chronic autoimmune inflammatory disorders arise following a breakdown in control of neutrophil activation and recruitment. In the search for new anti-inflammatory agents, we synthesized some new 2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives and tested them in vitro in order to evaluate their ability to interfere with human neutrophil functions. All tested compounds showed strong inhibition of fMLP-OMe-induced chemotaxis, although they appeared unable to block degranulation and the fMLP-OMe-induced respiratory burst, and were inactive in binding experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Binding, Competitive
  • Chemistry, Pharmaceutical / methods*
  • Chemotaxis / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Models, Chemical
  • N-Formylmethionine Leucyl-Phenylalanine / antagonists & inhibitors*
  • N-Formylmethionine Leucyl-Phenylalanine / chemistry*
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Protein Binding
  • Pyrazoles / chemistry*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Pyrazoles
  • N-Formylmethionine Leucyl-Phenylalanine
  • 2,3-dihydro-1H-imidazo(1,2-b)pyrazole