Ontology highlight
ABSTRACT:
SUBMITTER: Wood MR
PROVIDER: S-EPMC5304297 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Wood Michael R MR Noetzel Meredith J MJ Melancon Bruce J BJ Poslusney Michael S MS Nance Kellie D KD Hurtado Miguel A MA Luscombe Vincent B VB Weiner Rebecca L RL Rodriguez Alice L AL Lamsal Atin A Chang Sichen S Bubser Michael M Blobaum Anna L AL Engers Darren W DW Niswender Colleen M CM Jones Carrie K CK Brandon Nicholas J NJ Wood Michael W MW Duggan Mark E ME Conn P Jeffrey PJ Bridges Thomas M TM Lindsley Craig W CW
ACS medicinal chemistry letters 20161216 2
Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M<sub>4</sub>) positive allosteric modulators (PAMs). Compound <b>6c</b> (VU0467485) possesses robust <i>in vitro</i> M<sub>4</sub> PAM potency across species and <i>in vivo</i> efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, <b>6c</b> (VU0467485) was evaluated as a precl ...[more]