Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.
Basic Information
ID: ALA1139227
Journal: J Med Chem
Title: Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.
Authors: Chappie TA, Humphrey JM, Allen MP, Estep KG, Fox CB, Lebel LA, Liras S, Marr ES, Menniti FS, Pandit J, Schmidt CJ, Tu M, Williams RD, Yang FV.
Abstract: A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.
CiteXplore: 17228859
DOI: 10.1021/jm060653b
Patent ID: ┄