title: Development of prostaglandin D2 receptor antagonist: discovery of highly potent antagonists.
abstract: The process of discovery for highly potent prostaglandin D(2) (PGD(2)) receptor antagonists is reported. A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and identified as a new class of selective PGD(2) receptor antagonists. Most of them exhibited strong PGD(2) receptor antagonism in binding studies and the cAMP formation assay. The structure-activity relationships (SAR), including subtype selectivity of the synthesized compounds, 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.lastname: Masaaki Toda
mesh_terms: D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D007210:Indoleacetic Acids / Q000737:chemistry / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D018926:Anti-Allergic Agents; D007210:Indoleacetic Acids; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; C036293:prostaglandin D2 receptor