SECONDARY AMINE ANALOGS OF 3-BETA-(4'-SUBSTITUTED PHENYL)TROPANE-2-BETA-CARBOXYLIC ACID-ESTERS AND N-NORCOCAINE EXHIBIT ENHANCED AFFINITY FOR SEROTONIN AND NOREPINEPHRINE TRANSPORTERS

被引：97

作者：

BOJA, JW

KUHAR, MJ

KOPAJTIC, T

YANG, E

ABRAHAM, P

LEWIN, AH

CARROLL, FI

机构：

[1] RES TRIANGLE INST,RES TRIANGLE PK,NC 27709

[2] NIDA,ADDICT RES CTR,BALTIMORE,MD 21224

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 08期

关键词：

D O I：

10.1021/jm00034a021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.

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页码：1220 / 1223

页数：4

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