title: Development of a prostaglandin D2 receptor antagonist: discovery of a new chemical lead.
abstract: A series of N-(p-alkoxy)benzoyl-5-methoxy-2-methylindole-3-acetic acids and N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid were discovered as new chemical leads for a prostaglandin D2 (PGD2) receptor antagonist. Most of them exhibited PGD2 receptor binding and blocked cyclic adenosine 3',5'-monophosphate (cAMP) formation in vitro. In particular, 2-methylindole-4-acetic acid analog 1 showed markedly increased receptor affinity and cAMP antagonist activity. Chemistry and structure activity relationship (SAR) data are also presented.
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: Hiromu
authors.initials: H
authors.lastname: Egashira
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okada
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: D000818:Animals; D019540:Area Under Curve; D001667:Binding, Competitive / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D006207:Half-Life; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007213:Indomethacin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
chemical_list: D007210:Indoleacetic Acids; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D007213:Indomethacin; C036293:prostaglandin D2 receptor