文摘
Herein, we report the structure–activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (Mb>4b>) positive allosteric modulators (PAMs). Compound <b>6cb> (VU0467485) possesses robust in vitro Mb>4b> PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, <b>6cb> (VU0467485) was evaluated as a preclinical development candidate.