Methylation of imidazoline related compounds leads to loss of α2-adrenoceptor affinity. Synthesis and biological evaluation of selective I1 imidazoline receptor ligands

被引：13

作者：

Schann, Stephan ^{[1
]}

Greney, Hugues ^{[1
]}

Gasparik, Vincent ^{[1
]}

Dontenwill, Monique ^{[1
]}

Rascente, Carla ^{[1
]}

Lacroix, Gabriel ^{[1
]}

Monassier, Laurent ^{[1
]}

Bruban, Veronique ^{[1
]}

Feldman, Josiane ^{[1
]}

Ehrhardt, Jean-Daniel ^{[1
]}

Bousquet, Pascal ^{[1
]}

机构：

[1] Univ Strasbourg, Lab Neurobiol & Pharmacol Cardiovasc, EA 4438, Fac Med, F-67000 Strasbourg, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 15期

关键词：

Imidazolines; Clonidine; Rilmenidine; Alpha(2)-adrenoceptor; Hypotensive agents; I-2-IMIDAZOLINE BINDING-SITES; I-1-IMIDAZOLINE RECEPTORS; I1-IMIDAZOLINE SITES; CLONIDINE; AGONIST; ADRENOCEPTORS; RILMENIDINE; DERIVATIVES; HYPOTENSION; MOXONIDINE;

D O I：

10.1016/j.bmc.2012.06.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Methylated analogues of imidazoline related compounds (IRC) were prepared; their abilities to bind I-1 imidazoline receptors (I(1)Rs), I-2 imidazoline binding sites (I2BS) and alpha(2)-adrenoceptor subtypes (alpha(2)ARs) were assessed. Methylation of the heterocyclic moiety of IRC resulted in a significant loss of alpha(2)AR affinity. Amongst the selective ligands obtained, LNP 630 (4) constitutes the first highly selective I1R agent showing hypotensive activity after intravenous administration. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4710 / 4715

页数：6

共 4 条

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[3] Chronic ethanol administration attenuates imidazoline I1 receptor- or α2-adrenoceptor-mediated reductions in blood pressure and hemodynamic variability in hypertensive rats
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[4] Synthesis and Biological Evaluation of 2-Aryliminopyrrolidines as Selective Ligands for I1 lmidazoline Receptors: Discovery of New Sympatho-Inhibitory Hypotensive Agents with Potential Beneficial Effects in Metabolic Syndrome
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