SAR-based optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as highly potent EP1 receptor antagonists

被引：24

作者：

Atobe, Masakazu ^{[1
]}

Naganuma, Kenji ^{[1
]}

Kawanishi, Masashi ^{[1
]}

Morimoto, Akifumi ^{[1
]}

Kasahara, Ken-ichi ^{[1
]}

Ohashi, Shigeki ^{[1
]}

Suzuki, Hiroko ^{[1
]}

Hayashi, Takahiko ^{[1
]}

Miyoshi, Shiro ^{[1
]}

机构：

[1] Asahi Kasei Pharma Corp, Pharmaceut Res Ctr, Izunokuni, Shizuoka 4102321, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 24期

关键词：

EP1; antagonist; Pyrazole; Thiazole; Solubility; Optimization; URINARY-BLADDER; RATS;

D O I：

10.1016/j.bmcl.2013.10.065

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6569 / 6576

页数：8

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