Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS.
AUTHORS
Zhou
YYa ,
Rodriguez
AL Alice L ,
Williams
R Richard ,
Weaver
CD C David ,
Conn
PJ P Jeffrey ,
Lindsley
CW Craig W .
Bioorganic & medicinal chemistry letters. 2009 12 1; 19(23).
6502-6
- PMID: 19875287[PubMed].
- PMCID: PMC3177597.
- NIHMSID: NIHMS153224
ABSTRACT
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.