title: Discovery of a new class of potent, selective, and orally active prostaglandin D2 receptor antagonists.
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.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. torisu@ono.co.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Torisu
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Maki
authors.initials: M
authors.lastname: Iwahashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Onoda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagase
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Nanbu
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohuchida
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D007210:Indoleacetic Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D007210:Indoleacetic Acids; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor