Rhodamine-labeled 2β-carbomethoxy-3β-(3,4-dichlorophenyl)- tropane analogues as high-affinity fluorescent probes for the dopamine transporter

被引：44

作者：

Cha, JH

Zou, MF

Adkins, EM

Rasmussen, SGF

Loland, CJ

Schoenenberger, B

Gether, U

Newman, AH

机构：

[1] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] Univ Copenhagen, Panum Inst, Dept Pharmacol, Mol Pharmacol Grp, DK-2200 Copenhagen, Denmark

[3] Fluka GmbH, CH-9471 Buchs, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 24期

关键词：

D O I：

10.1021/jm050431y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane, using an ethylamino linker. The resulting 2-substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the highest DAT binding affinities expressed in COS-7 cells (K-i = 27 and 18 nM, respectively) in the series. Visualization of the DAT with 5 and 9 was demonstrated by confocal fluorescence laser scanning microscopy in stably transfected HEK293 cells.

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页码：7513 / 7516

页数：4

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