Bis(aminopyrrolidine)-derived ureas (APUs) as potent MCH1 receptor antagonists

被引：25

作者：

Grey, J

Dyck, B

Rowbottom, MW

Tamiya, J

Vickers, TD

Zhang, MZ

Zhao, LR

Heise, CE

Schwarz, D

Saunders, J

Goodfellow, VS

机构：

[1] Neurocrine Biosci Inc, Dept Med Chem, San Diego, CA 92130 USA

[2] Neurocrine Biosci Inc, Dept Pharmacol, San Diego, CA 92130 USA

[3] Neurocrine Biosci Inc, Dept Mol Biol, San Diego, CA 92130 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 04期

关键词：

melanin-concentrating hormone; obesity; anxiety; depression;

D O I：

10.1016/j.bmcl.2004.12.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ureas derived from two substituted 3-aminopyrrolidine subunits were prepared as constrained analogs of a linear lead compound and tested as antagonists of the MCH1 receptor. The series was optimized for substitution and stereochemistry to generate a functional antagonist with a K-i of 3.3 nM and IC50 of 12 nM (GTPgammaS). (C) 2004 Elsevier Ltd. All rights reserved.

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页码：999 / 1004

页数：6

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