Synthesis and biological evaluation of N-cyclopropylbenzamide-benzophenone hybrids as novel and selective p38 mitogen activated protein kinase (MAPK) inhibitors

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3694-8. doi: 10.1016/j.bmcl.2015.06.036. Epub 2015 Jun 16.

Abstract

A series of hybrid molecules consisting of benzophenones and N-cyclopropyl-3-methylbenzamides were synthesized and biologically evaluated as novel p38 mitogen activated protein kinase (MAPK) inhibitors. In particular, we found that compound 10g displayed potent p38α MAPK inhibitory activity (IC50=0.027 μM), high kinase selectivity, and significant anti-inflammatory activity in THP-1 monocyte cells.

Keywords: Benzophenone; Hybrid; Kinase selectivity; N-Cyclopropylbenzamide; P38 mitogen activated protein kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Benzamides / chemistry
  • Benzophenones / chemistry*
  • Cell Line / drug effects
  • Chemistry Techniques, Synthetic
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Inhibitory Concentration 50
  • Monocytes / drug effects
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzamides
  • Benzophenones
  • Protein Kinase Inhibitors
  • benzophenone
  • p38 Mitogen-Activated Protein Kinases