Synthesis, dopamine D2 receptor binding studies and docking analysis of 5-[3-(4-arylpiperazin-1-yl)propyl]-1H-benzimidazole, 5-[2-(4-arylpiperazin-1-yl)ethoxy]-1H-benzimidazole and their analogs
Synthesis, dopamine D2 receptor binding studies and docking analysis of 5-[3-(4-arylpiperazin-1-yl)propyl]-1H-benzimidazole, 5-[2-(4-arylpiperazin-1-yl)ethoxy]-1H-benzimidazole and their analogs
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DOI：
10.1016/j.ejmech.2004.10.006
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发表时间：
2005-05-01
影响因子：
6.7
通讯作者：
Soskic, V
中科院分区：
文献类型：
--
作者：
Sukalovic, V;Andric, D;Soskic, V
合成了5-[3-（4-芳基哌嗪-1-基）丙基]-1H-苯并咪唑和5-[2-（4-芳基哌嗪-1-基）乙氧基]-1H-苯并咪唑，并测定了它们对D-1、D-2和5-HT_（1A）受体的亲和力。它们对D-2多巴酚丁胺受体表达相当高的亲和力。通过对接分析揭示的配体-D-2受体相互作用的主要特征是：哌嗪环质子化N-1与Asp 86之间的盐桥，配体苯并咪唑部分与Ser 141、Ser 122和His 189之间的氢键，芳基哌嗪芳环与Phe 178之间的边-面相互作用，Tyr 216和Trp 182之间的氢键以及乙烯氧基配体中的醚氧与Phe 185或Trp 115的氢之间的氢键。活性最高的5-{2-[4-（2-甲氧基苯基）-哌嗪-1-基]乙氧基}-1，3-二氢-2H-苯并咪唑-2-基（27）具有最大数量的吸引相互作用。观察到化合物对接到D-2受体和竞争结合结果之间的令人满意的相关性。(c)2005年，Elsevier SAS。All rights reserved.
5-[3-(4-Arylpiperazin-1-yl)propyl]-1H-benzimidazoles and 5-[2-(4-aryipiperazin-1-yl)ethoxy]-1H-benzimidazoles were synthesized and their affinity for the D-1, D-2 and 5-HT1A, receptors examined. They expressed a rather high affinity for the D-2 doparnine receptor. The main features of ligand-D-2 receptor interactions revealed by docking analyses were: salt bridge between piperazine ring protonated N-1 and Asp 86, hydrogen bonds of ligand bezimidazole part with Ser 141, Ser 122 and His 189, edge-to-face interactions of arylpiperazine aromatic ring with Phe 178, Tyr 216 and Trp 182 and hydrogen bond between ethereal oxygen in ethylenoxy ligands and hydrogen of Phe 185 or Trp 115. The most active 5-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethoxy}-1,3-di hydro-2H-benzimidazole-2-thione (27) has a maximal number of attractive interactions. A satisfactory correlation between docking of the compounds into the D-2 receptor and competition binding results was observed. (c) 2005 Elsevier SAS. All rights reserved.