Discovery of a new class of potent, selective, and orally active prostaglandin D2 receptor antagonists

Bioorg Med Chem. 2004 Oct 15;12(20):5361-78. doi: 10.1016/j.bmc.2004.07.048.

Abstract

The process of discovering a series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acid analogs is presented since these compounds represent a new class of potent, selective, and orally active prostaglandin D2 (PGD2) receptor antagonists. Most of these compounds exhibit strong PGD2 receptor binding and PGD2 receptor antagonism in cAMP formation assays. When given orally, these new antagonists dramatically suppress allergic inflammatory responses, such as the PGD2-induced or OVA-induced increase of vascular permeability. Structure-activity relationship (SAR) data are also discussed.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / chemistry*
  • Anti-Allergic Agents / pharmacology*
  • Guinea Pigs
  • Humans
  • Indoleacetic Acids / administration & dosage
  • Indoleacetic Acids / chemistry*
  • Indoleacetic Acids / pharmacology*
  • Rats
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism

Substances

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