Ontology highlight
ABSTRACT:
SUBMITTER: Bollinger KA
PROVIDER: S-EPMC5601377 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Bollinger Katrina A KA Felts Andrew S AS Brassard Christopher J CJ Engers Julie L JL Rodriguez Alice L AL Weiner Rebecca L RL Cho Hyekyung P HP Chang Sichen S Bubser Michael M Jones Carrie K CK Blobaum Anna L AL Niswender Colleen M CM Conn P Jeffrey PJ Emmitte Kyle A KA Lindsley Craig W CW
ACS medicinal chemistry letters 20170803 9
Herein, we detail the optimization of the mGlu<sub>2</sub> negative allosteric modulator (NAM), VU6001192, by a reductionist approach to afford a novel, simplified mGlu<sub>2</sub> NAM scaffold. This new chemotype not only affords potent and selective mGlu<sub>2</sub> inhibition, as exemplified by VU6001966 (mGlu<sub>2</sub> IC<sub>50</sub> = 78 nM, mGlu<sub>3</sub> IC<sub>50</sub> > 30 μM), but also excellent central nervous system (CNS) penetration (<i>K</i><sub>p</sub> = 1.9, <i>K</i><sub>p,u ...[more]