14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: Design, synthesis, and biological studies
14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: Design, synthesis, and biological studies
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DOI：
10.1016/j.bmcl.2008.12.093
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发表时间：
2009-03-15
影响因子：
2.7
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Li, Guo;Aschenbach, Lindsey C. K.;Zhang, Yan
μ阿片受体拮抗剂具有临床实用性，是重要的研究工具。为了开发非肽类高选择性μ阿片受体拮抗剂，设计、合成了一系列14-O-杂环取代的纳洛酮衍生物，并对其进行了评价。这些化合物显示出亚纳摩尔至纳摩尔的μ阿片受体结合亲和力。其中，化合物1对μ阿片受体的选择性最高，而对δ和κ受体的选择性最低。这些结果暗示了μ阿片受体的细胞外环中的替代“地址”结构域。(C)2008爱思唯尔有限公司保留所有权利。
Mu opioid receptor antagonists have clinical utility and are important research tools. To develop non-peptide and highly selective mu opioid receptor antagonist, a series of 14-O-heterocyclic-substituted naltrexone derivatives were designed, synthesized, and evaluated. These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. Among them, compound 1 exhibited the highest selectivity for the mu opioid receptor over the delta and kappa receptors. These results implicated an alternative 'address' domain in the extracellular loops of the mu opioid receptor. (C) 2008 Elsevier Ltd. All rights reserved.