Challenges in the development of mGluR5 positive allosteric modulators: The discovery of CPPHA

被引：66

作者：

Zhao, Zhijian

Wisnoski, David D.

O'Brien, Julie A.

Lemaire, Wei

Williams, David L., Jr.

Jacobson, Marlene A.

Wittman, Marion

Ha, Sookhee N.

Schaffhauser, Herve

Sur, Cyrille

Pettibone, Doug J.

Duggan, Mark E.

Conn, P. Jeffrey

Hartman, George D.

Lindsley, Craig W.

机构：

[1] Merck & Co Inc, Dept Med Chem, West Point, PA 19486 USA

[2] Merck & Co Inc, Dept Neurosci, West Point, PA 19486 USA

[3] Vanderbilt Univ, Med Ctr, Dept Pharmacol, VICB Program Drug Discovery, Nashville, TN 37232 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

D O I：

10.1016/j.bmcl.2006.11.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor rnGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs, CPPHA has been the focus of numerous pharmacology studies by several laboratories. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1386 / 1391

页数：6

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