5-(Pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl) indazoles as MCH-1 antagonists

被引：17

作者：

Surman, Matthew D. ^{[1
]}

Freeman, Emily E. ^{[1
]}

Grabowski, James F. ^{[1
]}

Hadden, Mark ^{[1
]}

Henderson, Alan J. ^{[1
]}

Jiang, Guowei ^{[1
]}

Jiang, Xiaowu ^{[1
]}

Luche, Michele ^{[1
]}

Khmelnitsky, Yuri ^{[1
]}

Vickers, Steven ^{[2
]}

Viggers, Jean ^{[2
]}

Cheetham, Sharon ^{[2
]}

Guzzo, Peter R. ^{[1
]}

机构：

[1] AMRI, Albany, NY 12212 USA

[2] RenaSci Consultancy Ltd, Bioc, Nottingham NG1 1GF, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 23期

关键词：

Melanin concentrating hormone; MCH-1; antagonists; Obesity; Indazoles; HORMONE-RECEPTOR ANTAGONISTS; OBESITY; RISK; DISCOVERY; WOMEN;

D O I：

10.1016/j.bmcl.2010.09.039

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A new series of 5-(pyridinon-1-yl)indazoles with MCH-1 antagonist activity were synthesized. Potential cardiovascular risk for these compounds was assessed based upon their interaction with the hERG potassium channel in a mini-patch clamp assay. Selected compounds were studied in a 5-day diet-induced obese mouse model to evaluate their potential use as weight loss agents. Structural modification of the 5-(pyridinon-1-yl) indazoles to give 5-(furopyridinon-5-yl) indazoles provided compounds with enhanced pharmacokinetic properties and improved efficacy. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7015 / 7019

页数：5

共 20 条

[1]

The obesity epidemic [J].