An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine transporter

被引：10

作者：

Lowe, John A., III ^{[1
]}

DeNinno, Shari L. ^{[1
]}

Drozda, Susan E. ^{[1
]}

Schmidt, Christopher J. ^{[1
]}

Ward, Karen M. ^{[1
]}

Tingley, F. David, III ^{[1
]}

Sanner, Mark ^{[1
]}

Tunucci, Don ^{[1
]}

Valentine, James ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

Glycine; Transporter; Inhibitor; Schizophrenia;

D O I：

10.1016/j.bmcl.2009.12.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：907 / 911

页数：5

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