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