Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.

Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.

Bioorganic & medicinal chemistry letters (2009-10-31)

Ya Zhou, Alice L Rodriguez, Richard Williams, C David Weaver, P Jeffrey Conn, Craig W Lindsley

PMID19875287

摘要

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 identified by a functional HTS approach. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold.