Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives

被引：24

作者：

El Aouad, Noureddine ^{[1
]}

Berenguer, Inmaculada ^{[1
]}

Romero, Vanessa ^{[1
]}

Marin, Paloma ^{[1
]}

Serrano, Angel ^{[1
]}

Andujar, Sebastian ^{[2
,3
]}

Suvire, Fernando ^{[2
]}

Bermejo, Almudena ^{[1
,4
]}

Dolores Ivorra, M. ^{[1
]}

Enriz, Ricardo D. ^{[2
,3
]}

Cabedo, Nuria ^{[1
,5
]}

Cortes, Diego ^{[1
]}

机构：

[1] Univ Valencia, Fac Farm, Dept Farmacol, Valencia 46100, Spain

[2] Univ Nacl San Luis, Dept Quim, San Luis, Argentina

[3] Consejo Nacl Invest Cient & Tecn, IMIBIO SL, RA-5700 San Luis, Argentina

[4] IVIA, Dept Citricultura, Valencia 46113, Spain

[5] Univ Politecn Valencia, Inst Agroforestal Mediterraneo, Ctr Ecol Quim Agr, Valencia 46022, Spain

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

关键词：

1-Halogenated benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines; Binding; Dopamine receptors; Dopamine uptake; Structure-activity relationships; N-ALKYL-BENZYLTETRAHYDROISOQUINOLINES; ISOQUINOLINE ALKALOIDS; RECEPTOR; ANTAGONISTS; MECHANISM;

D O I：

10.1016/j.ejmech.2009.06.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D-1-like and/or D-2-like dopamine receptors in striatal membranes, although they were unable to inhibit [H-3]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K-i values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4616 / 4621

页数：6

共 15 条

[1] Syntheses of dopaminergic 1-cyclohexylmethyl-7,8-dioxygenated tetrahydroisoquinolines by selective heterogeneous tandem hydrogenation [J].