Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel glass of monoamine transporter inhibitors

被引：46

作者：

Enyedy, IJ

Zaman, WA

Sakamuri, S

Kozikowski, AP

Johnson, KM

Wang, SM

机构：

[1] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA

[2] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA

[3] Univ Texas, Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA

[4] Georgetown Univ, Med Ctr, Dept Neurol, Drug Discovery Program, Washington, DC 20007 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 09期

关键词：

D O I：

10.1016/S0960-894X(01)00132-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3.4-Disubstituted pyrrolidines were discovered as a novel class of monoamine transporter inhibitors through 3-D database pharmacophore searching using a new pharmacophore model. The most potent analogue 12 has K-i values of 0.084 muM in [H-3]mazindol binding, 0.20, 0.23, and 0.031 muM in inhibition of dopamine (DA), serotonin (SER), and norepinephrine (NE) reuptake, respectively. Functional antagonism testing in vitro showed that 11 and 12 are weak cocaine antagonists. (C) 2001 Elsevier Science Ltd. All rights reserved.

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页码：1113 / 1118

页数：6

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