Discovery of novel pyrazolo[1,5-a]pyridine-based EP1 receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships

被引：17

作者：

Nishigaya, Yosuke ^{[1
]}

Umei, Kentaro ^{[1
]}

Saito, Yoshifumi ^{[1
]}

Watanabe, Hiroyuki ^{[1
]}

Kondo, Tatsuhiro ^{[2
]}

Kondo, Atsushi ^{[2
]}

Kawamura, Naohiro ^{[2
]}

Tatani, Kazuya ^{[2
]}

Kohno, Yasushi ^{[1
]}

Tanaka, Nobuyuki ^{[2
]}

Seto, Shigeki ^{[1
]}

机构：

[1] Kyorin Pharmaceut Co Ltd, Watarase Res Ctr, Discovery Res Headquarters, 1848,Nogi, Nogi, Tochigi 3290114, Japan

[2] Kissei Pharmaceut Co Ltd, Cent Res Labs, 4365-1,Kashiwabara, Nagano 3998304, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 17期

关键词：

Scaffold-hopping; Pyrazolo[1,5-a]pyridine; Structure-activity relationships; EP1; antagonist; 2-(1H-PYRAZOL-1-YL)-THIAZOLE DERIVATIVES; BIOLOGICAL EVALUATION; PROSTANOID RECEPTORS; OPTIMIZATION; IDENTIFICATION; SUBTYPES; POTENT; ACID; RATS; CLASSIFICATION;

D O I：

10.1016/j.bmcl.2017.07.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A scaffold-hopping strategy towards a new pyrazolo[1,5-a]pyridine based core using molecular hybridization of two structurally distinct EP1 antagonists, followed by structure-activity relationship guided optimization, resulted in the identification of potent EP1 antagonists exemplified by 4c, 4f, and 4j, which were shown to reduce pathological intravesical pressure in rats when administered at 1 mg/kg iv. (C) 2017 Published by Elsevier Ltd.

引用

页码：4044 / 4050

页数：7

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