title: Discovery of heteroaryl sulfonamides as new EP1 receptor selective antagonists.
abstract: 4-({2-[Isobutyl(phenylsulfonyl)amino]-5-(trifluoromethyl)phenoxy}methyl)benzoic acid (1) is a functional PGE2 antagonist selective for EP1 receptor subtype. Analogs of 1, in which the phenyl-sulfonyl moiety has been replaced with more hydrophilic heteroarylsulfonyl moieties, exhibited more optimized antagonist activity, while some of them showed in vivo antagonist activity. Structure-activity relationship (SAR) studies are also presented.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. naganawa@ono.co.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Saito
authors.forename: Masaki
authors.initials: M
authors.lastname: Ima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohuchida
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Kigen
authors.initials: K
authors.lastname: Kondo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000527:Alprostadil / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D010084:Oxidation-Reduction; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects
chemical_list: D007202:Indicators and Reagents; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides; C016767:sulprostone; D000527:Alprostadil; D015232:Dinoprostone