Discovery of orally active prostaglandin D2 receptor antagonists

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4891-5. doi: 10.1016/j.bmcl.2004.07.039.

Abstract

A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D(2) (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Allergic Agents / chemical synthesis*
  • Anti-Allergic Agents / pharmacology
  • Capillary Permeability
  • Guinea Pigs
  • Humans
  • Mice
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anti-Allergic Agents
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor