Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective ligands
Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective ligands
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DOI：
10.1016/s0968-0896(00)00280-7
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发表时间：
2001-03-01
影响因子：
3.5
通讯作者：
Renard, P
中科院分区：
文献类型：
--
作者：
Anastassiadou, M;Danoun, S;Renard, P
已经制备了几个系列的2-芳基或杂环-咪唑啉化合物，并在体外作为咪唑啉位点（I-1和I-2）和α-肾上腺素能（α（1）和α（2））受体配体进行了评价。它们的pK（i）值表明咪唑啉部分在2-位与芳族取代基的连接显著降低α-肾上腺素能亲和力。I-1位点更容易被在邻位或Meta位被甲基或甲氧基取代的苯基咪唑啉接近。事实上，2-（2 '-甲氧基苯基）-咪唑啉（17）是迄今报道的最好的I-1配体之一（pK（i）= 8.53和I-1/I-2 > 3388）。另一方面，在帕拉存在甲基时，I-2选择性增加。2-（3 '-氟-4'-甲苯基）-咪唑啉（31）是一种新的有效的I-2位配体，具有高选择性（pK（i）= 8.53，I-2/I-1 > 3388）。(C)2001爱思唯尔科技有限公司版权所有。
Several series of 2-aryl or heterocyclic-imidazoline compounds have been prepared and evaluated in vitro as imidazoline sites (I-1 and I-2) and alpha -adrenergic (alpha (1) and alpha (2)) receptor ligands. Their pK(i) values indicate that linkage of the imidazoline moiety at the 2-position with an aromatic substituent dramatically decreases alpha -adrenergic affinity. I-1 sites are more accessible by phenyl imidazolines substituted by a methyl or a methoxy group at the ortho or meta position. Indeed, 2-(2'-methoxyphenyl)-imidazoline (17) is one of the best I-1 ligands ever reported (pK(i) = 8.53 and I-1/I-2 > 3388). On the other hand, I-2 selectivity increases in the presence of a methyl group in the para position. The original compound, 2-(3'-fluoro-4'-tolyl)-imidazoline (31) is a new potent ligand for the I-2 sites with high selectivity (pK(i) = 8.53 and I-2/I-1 > 3388). (C) 2001 Elsevier Science Ltd. All rights reserved.