Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.

ID: ALA4371089

Journal: Bioorg Med Chem Lett

Title: Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.

Authors: Geneste H, Drescher K, Jakob C, Laplanche L, Ochse M, Torrent M.

Abstract: Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.

CiteXplore: 30587449

DOI: 10.1016/j.bmcl.2018.12.029

Patent ID: ┄