Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype

详细信息    查看全文

• 作者：Alice L. Rodriguez ; Richard Williams ; Ya Zhou ; Stacey R. Lindsley ; Uyen Le ; Mark D. Grier ; C. David Weaver ; P. Jeffrey Conn ; Craig W. Lindsley
• 关键词：mGluR5 ; Metabotropic ; Glutamate
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 June 2009
• 年：2009
• 卷：19
• 期：12
• 页码：3209-3213
• 全文大小：1465 K

文摘

This Letter describes the discovery and SAR of three novel series of mGluR5 non-competitive antagonists/negative allosteric modulators (NAMs) not based on manipulation of an MPEP/MTEP chemotype. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and the first example of a mode of pharmacology ‘switch’ to provide PAMs with a non-MPEP scaffold.