title: SAR-based optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as highly potent EP1 receptor antagonists.
abstract: We describe a medicinal chemistry approach for generating a series of 2-(1H-pyrazol-1-yl)thiazoles as EP1 receptor antagonists. To improve the physicochemical properties of compound 1, we investigated its structure-activity relationships (SAR). Optimization of this lead compound provided small compound 25 which exhibited the best EP1 receptor antagonist activity and a good SAR profile.
authors.affiliation: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. Electronic address: atobe.mb@om.asahi-kasei.co.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Atobe
authors.forename: Kenji
authors.initials: K
authors.lastname: Naganuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawanishi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Morimoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kasahara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011720:Pyrazoles; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013844:Thiazoles; C031280:pyrazole
keywords: EP1 antagonist; Optimization; Pyrazole; Solubility; Thiazole