Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding
Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding
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DOI：
10.1016/s0376-8716(99)00152-0
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发表时间：
2000-08-01
影响因子：
4.2
通讯作者：
Martin, BR
中科院分区：
文献类型：
--
作者：
Aung, MM;Griffin, G;Martin, BR
氨基烷基吲哚类似物（AAI）的N-1烷基侧链与大麻素CB 1受体的三点相互作用之一。在本研究中，WIN 55，212 -2的吗啉代乙基被从甲基到庚基的不同长度的碳链取代。在分子的萘甲酰基和C2位上添加额外的基团。这些结构变化表明，与CB 1和CB 2受体的高亲和力结合需要至少三个碳的烷基链长度，与两种受体的最佳结合发生在五个碳的侧链上。3-6个碳的烷基链足以进行高亲和力结合;然而，链延伸至庚基导致在两种受体处的结合显著降低。大麻拟吲哚的独特结构提供了一个有用的工具来定义在大麻素受体的配体-受体相互作用，并完善提出的药效团模型。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The N-1 alkyl side chain of the aminoalkylindole analogues (AAI) has been implicated as one of a three-point interaction with the cannabinoid CB1 receptor. In this study, the morpholinoethyl of WIN 55,212-2 was replaced with carbon chains of varying lengths ranging from a methyl to heptyl group. Additional groups were added to the naphthoyl and the C2 positions of the molecule. These structural changes revealed that high affinity binding to the CB1 and CB2 receptors requires an alkyl chain length of at least three carbons with optimum binding to both receptors occurring with a five carbon side chain. An alkyl chain of 3-6 carbons is sufficient for high affinity binding; however, extension of the chain to a heptyl group results in a dramatic decrease in binding at both receptors. The unique structure of the cannabimimetic indoles provides a useful tool to define the ligand-receptor interaction at both cannabinoid receptors and to refine proposed pharmacophore models. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.