Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases

Bioorg Med Chem Lett. 2011 Jan 1;21(1):288-93. doi: 10.1016/j.bmcl.2010.11.015. Epub 2010 Nov 5.

Abstract

In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.

MeSH terms

  • Animals
  • Carbolines / chemistry*
  • Carbolines / pharmacokinetics
  • Carbolines / therapeutic use
  • Humans
  • Lung Diseases / drug therapy*
  • Macaca mulatta
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism
  • Structure-Activity Relationship

Substances

  • ((7R)-7-(((4-fluorophenyl)sulfonyl)(methyl)amino)-6,7,8,9-tetrahydropyrido(1,2-a)indol-10-yl)acetic acid
  • Carbolines
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor