Evolution of novel tricyclic CRTh2 receptor antagonists from a (E)-2-cyano-3-(1H-indol-3-yl)acrylamide scaffold

Bioorg Med Chem Lett. 2013 Feb 15;23(4):944-8. doi: 10.1016/j.bmcl.2012.12.050. Epub 2012 Dec 25.

Abstract

(E)-2-(3-(3-((3-Bromophenyl)amino)-2-cyano-3-oxoprop-1-en-1-yl)-1H-indol-1-yl)acetic acid (1) was discovered in a HTS campaign for CRTh2 receptor antagonists. An SAR around this hit could be established and representatives with interesting activity profiles were obtained. Ring closing tactics to convert this hit series into a novel 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole based CRTh2 receptor antagonist series is presented.

MeSH terms

  • Acrylamides / chemistry*
  • Acrylamides / pharmacology*
  • Animals
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Models, Molecular
  • Rats
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Acrylamides
  • Indoles
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor