title: Discovery of 2-(1H-indazol-1-yl)-thiazole derivatives as selective EP(1) receptor antagonists for treatment of overactive bladder by core structure replacement.
abstract: We have designed a series of potent EP1 receptor antagonists. These antagonists are a series of 2-(1H-indazol-1-yl)-thiazoles in which the core structure was replaced with pyrazole-phenyl groups. In preliminary conscious rat cystometry experiments, two representative candidates, 2 and 22, increased bladder capacity. In particular, the increase using 22 was approximately 2-fold that of the baseline. More detailed profiling of this compound and further optimization of this series promises to provide a novel class of drug for treating overactive bladder (OAB).
authors: 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: Masakazu
authors: M
authors: Atobe
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Kenji
authors: K
authors: Naganuma
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Masashi
authors: M
authors: Kawanishi
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Akifumi
authors: A
authors: Morimoto
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Ken-ichi
authors: K
authors: Kasahara
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Shigeki
authors: S
authors: Ohashi
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Hiroko
authors: H
authors: Suzuki
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Takahiko
authors: T
authors: Hayashi
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors: Shiro
authors: S
authors: Miyoshi
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D006801:Humans; D007191:Indazoles / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001743:Urinary Bladder / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
chemical_list: D007191:Indazoles; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013844:Thiazoles
keywords: Cystometry; EP(1) antagonist; Indazole; Overactive bladder; Thiazole