QSAR study and synthesis of new phenyltropanes as ligands of the dopamine transporter (DAT)

被引：10

作者：

Mavel, Sylvie ^{[1
,2
]}

Mincheva, Zoya ^{[1
]}

Meheux, Nathalie ^{[1
]}

Carcenac, Yvan ^{[3
]}

Guilloteau, Denis ^{[1
,2
]}

Abarbri, Mohamed ^{[3
]}

Emond, Patrick ^{[1
,2
]}

机构：

[1] Univ Tours, INSERM U930, CNRS ERL3106, Tours, France

[2] Hop Bretonneau, CHRU, INSERM U930, F-37000 Tours, France

[3] Univ Tours, Fac Sci, Lab Physicochim Mat & Biomol EA 4244, F-37200 Tours, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 04期

关键词：

Dopamine transporter; Iodine; 3D-QSAR; Tropane; PHARMACOLOGICAL CHARACTERIZATION; PARKINSONS-DISEASE; HIGH-AFFINITY; COCAINE; SYSTEM; SPECT; RECEPTORS; ANALOGS; BINDING; IODINE-123-BETA-CIT;

D O I：

10.1016/j.bmc.2012.01.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The dopamine transporter (DAT) plays a pivotal role in the regulation of dopamine neurotransmission, and is involved in a number of physiological functions and brain disorders. Furthermore the DAT analysis by molecular imaging techniques is a useful tool for the diagnosis and follow up treatment of diseases involving the DAT. In order to predict the affinity of new derivatives for the DAT, different QSAR molecular modeling models based on cocaine were compared. We have evaluated in these models tropane derivatives synthesized with original synthons which coupled properties of both fluorine and iodine atoms. One compound showed a high in vitro affinity and selectivity for the DAT (K-i = 0.87 +/- 0.04 nM). This compound should be radiolabeled with radioiodine for further investigations by SPECT. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1388 / 1395

页数：8

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