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Weaver Lab

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

AUTHORS

Rodriguez ALAlice L , Williams R Richard , Zhou Y Ya , Lindsley SR Stacey R , Le U Uyen , Grier MD Mark D , Weaver CD C David , Conn PJ P Jeffrey , Lindsley CW Craig W . Bioorganic & medicinal chemistry letters. 2009 6 15; 19(12). 3209-13

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. 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.

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.