Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold.
AUTHORS
Williams
RRichard ,
Manka
JT Jason T ,
Rodriguez
AL Alice L ,
Vinson
PN Paige N ,
Niswender
CM Colleen M ,
Weaver
CD C David ,
Jones
CK Carrie K ,
Conn
PJ P Jeffrey .
Bioorganic & medicinal chemistry letters. 2011 3 1; 21(5).
1350-3
- PMID: 21315585[PubMed].
- PMCID: PMC3498823.
- NIHMSID: NIHMS266642
ABSTRACT
This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. ‘Molecular switches’ were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents.