Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors

被引：111

作者：

Chappie, Thomas A. ^{[1
]}

Humphrey, John M. ^{[1
]}

Allen, Martin P. ^{[1
]}

Estep, Kimberly G. ^{[1
]}

Fox, Carol B. ^{[1
]}

Lebel, Lorraine A. ^{[1
]}

Liras, Spiros ^{[1
]}

Marr, Eric S. ^{[1
]}

Menniti, Frank S. ^{[1
]}

Pandit, Jayvardhan ^{[1
]}

Schmidt, Christopher J. ^{[1
]}

Tu, Meihua ^{[1
]}

Williams, Robert D. ^{[1
]}

Yang, Feng V. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, CNS Discovery & Expt Med Sci, Groton, CT 06340 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 02期

关键词：

D O I：

10.1021/jm060653b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. © 2007 American Chemical Society.

引用

页码：182 / 185

页数：4

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