Download MendeleyDiscovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors
Chappie, T.A., Humphrey, J.M., Allen, M.P., Estep, K.G., Fox, C.B., Lebel, L.A., Liras, S., Marr, E.S., Menniti, F.S., Pandit, J., Schmidt, C.J., Tu, M., Williams, R.D., Yang, F.V.(2007) J Med Chem 50: 182-185
- PubMed: 17228859
- DOI: https://doi.org/10.1021/jm060653b
- Primary Citation of Related Structures:
2O8H, 2OVV, 2OVY - PubMed 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.
Organizational Affiliation:
CNS Discovery and Experimental Medicinal Sciences, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. thomas.a.chappie@pfizer.com
