Synthesis and biological evaluation of 3-alkyl-dihydrotetrabenazine derivatives as vesicular monoamine transporter-2 (VMAT2) ligands

被引：8

作者：

Zheng, Pinguan ^{[1
]}

Lieberman, Brian P. ^{[1
]}

Choi, Seok Rye ^{[2
]}

Ploeessl, Karl ^{[1
]}

Kung, Hank F. ^{[1
,3
]}

机构：

[1] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA

[2] Avid Radiopharmaceut, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 11期

关键词：

Dihydrotetrabenazine; Vesicular monoamine transporter; Parkinson's disease; Positron emission tomography; POSITRON-EMISSION-TOMOGRAPHY; TETRABENAZINE; DIHYDROTETRABENAZINE; BINDING; CLONING;

D O I：

10.1016/j.bmcl.2011.03.113

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the search of new probes for in vivo brain imaging of vesicular monoamine transporter type 2 (VMAT2), we have developed an efficient synthesis of a novel series of 3-alkyl-dihydrotetrabenazine (DTBZ) derivatives. The affinity of VMAT2 was evaluated by an in vitro inhibitory binding assay using [I-125]-iodovinyl-TBZ or [F-18](+)-FP-DTBZ as radioligands in rat striatal tissue homogenates. New DTBZ derivatives exhibited moderate to good binding affinity to VMAT2. Among these new ligands, compound 4b showed the best affinity for VMAT2 (K-i = 5.98 nM) and may be a useful lead compound for future structure-activity studies. (C) 2011 Published by Elsevier Ltd.

引用

页码：3435 / 3438

页数：4

共 35 条

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