N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide:: A potent and selective dopamine D4 ligand

被引：22

作者：

Perrone, R ^{[1
]}

Berardi, F ^{[1
]}

Colabufo, NA ^{[1
]}

Leopoldo, M ^{[1
]}

Tortorella, V ^{[1
]}

机构：

[1] Univ Bari, Dipartimento Farmaco Chim, I-70126 Bari, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 24期

关键词：

D O I：

10.1021/jm981041x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new 1-aryl-4-alkylpiperazines containing a terminal benzamide fragment or a tetralin-1-yl nucleus on the alkyl chain were synthesized and tested for binding at cloned human dopamine D-4 and D-2 receptor subtypes. A SAFIR (structure-affinity relationship) study on this series is herein discussed. The most relevant D-4 receptor affinities were displayed by N-[omega-[4-arylpiperazin-1-yl]alkyl]-methoxybenzamides (compounds 5, 16-20), their IC50 values ranging between 0.057 and 7.8 nM. Among these, N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (17) emerged since it exhibited very high affinity for dopamine D-4 receptor (IC50 = 0.057 nM) with selectivity of >10 000 for the D-4 versus the D-2 receptor; compound 17 was also selective versus serotonin 5-HT1A and adrenergic alpha(1) receptors.

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页码：4903 / 4909

页数：7

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