THE DISCOVERY OF AN UNUSUALLY SELECTIVE AND NOVEL COCAINE ANALOG - DIFLUOROPINE - SYNTHESIS AND INHIBITION OF BINDING AT COCAINE RECOGNITION SITES

被引：98

作者：

MELTZER, PC

LIANG, AY

MADRAS, BK

机构：

[1] HARVARD UNIV, SCH MED, DEPT PSYCHIAT, SOUTHBOROUGH, MA 01772 USA

[2] NEW ENGLAND REG PRIMATE RES CTR, SOUTHBOROUGH, MA 01772 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 13期

关键词：

D O I：

10.1021/jm00039a014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cocaine is a stimulant drug with a high abuse liability. Although it inhibits several monamine transporters in the mammalian brain, its primary mechanism of action has been ascribed to its inhibition of the dopamine transporter. The synthesis, characterization, and receptor binding properties of all eight isomers of a unique tropane analog, 2-carbomethoxy-3-[bis(4-fluorophenyl)methoxy]tropane is described. In addition, we report that the S-enantiomer, (S)-(+)-2 beta-carbomethoxy-3 alpha-[bis(4-fluorophenyl)methoxy]tropane, Difluoropine, is a potent (IC50 10.9 nM) and selective (324 [DA/5HT]) ligand for the dopamine transporter.

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页码：2001 / 2010

页数：10

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