Discovery of VU0467485/AZ13713945: An M₄ PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia.

ABSTRACT: Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M₄) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M₄ 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.

SUBMITTER: Wood MR 

PROVIDER: S-EPMC5304297 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature