Discovery of 4-[1-[([1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl]carbonyl)amino]cyclopropyl]benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory pain

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3760-3. doi: 10.1016/j.bmcl.2010.04.065. Epub 2010 Apr 18.

Abstract

The discovery of a highly potent and selective EP(4) antagonist MF-766 is discussed. This N-benzyl indole derivative exhibits good pharmacokinetic profile and unprecedented in vivo potency in the rat AIA model.

MeSH terms

  • Animals
  • Arthritis / drug therapy
  • Benzoates / chemistry
  • Benzoates / pharmacology*
  • Benzoates / therapeutic use
  • Cells, Cultured
  • Dogs
  • Drug Discovery
  • Drug Stability
  • Hepatocytes
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Inflammation / drug therapy
  • Pain / drug therapy*
  • Pharmacokinetics
  • Rats
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E, EP4 Subtype
  • Structure-Activity Relationship

Substances

  • Benzoates
  • Indoles
  • PTGER4 protein, human
  • Ptger4 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype