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

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 D-2 (PGD(2)) receptor antagonists. Most of these compounds exhibit strong PGD(2) receptor binding and PGD(2) receptor antagonism in cAMP formation assays. When given orally, these new antagonists dramatically suppress allergic inflammatory responses, such as the PGD(2)-induced or OVA-induced increase of vascular permeability. Structure-activity relationship (SAR) data are also discussed. (C) 2004 Elsevier Ltd. All rights reserved.