Discovery of a Series of 6,7-Dimethoxy-4-pyrrolidylquinazoline PDE10A Inhibitors
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- 作者：Thomas A. Chappie ; John M. Humphrey ; Martin P. Allen ; Kimberly G. Estep ; Carol B. Fox ; Lorraine A. Lebel ; Spiros Liras ; Eric S. Marr ; Frank S. Menniti ; Jayvardhan Pandit ; Christopher J. Schmidt ; Meihu
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：January 25, 2007
- 年：2007
- 卷：50
- 期：2
- 页码：182 - 185
- 全文大小：259K
- 年卷期：v.50,no.2(January 25, 2007)
- ISSN：1520-4804
文摘
A papaverine based pharmacophore model for PDE10Ainhibition was generated via SBDD and used to design a library of4-amino-6,7-dimethoxyquinazolines. From this library emerged an arylether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focalpoint for additional modeling, X-ray, and synthetic efforts towardincreasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selectivebrain penetrable inhibitor of PDE10A.