Li Guo, Aschenbach Lindsey C K, He Hengjun, Selley Dana E, Zhang Yan
Department of Medicinal Chemistry, Virginia Commonwealth University, 410 North 12th Street, PO Box 980613, Richmond, VA 23298-0613, USA.
Bioorg Med Chem Lett. 2009 Mar 15;19(6):1825-9. doi: 10.1016/j.bmcl.2008.12.093. Epub 2008 Dec 29.
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.
μ阿片受体拮抗剂具有临床应用价值且是重要的研究工具。为开发非肽类且高度选择性的μ阿片受体拮抗剂，设计、合成并评估了一系列14 - O - 杂环取代的纳曲酮衍生物。这些化合物对μ阿片受体表现出纳摩尔以下至纳摩尔级别的结合亲和力。其中，化合物1对μ阿片受体相对于δ和κ受体表现出最高的选择性。这些结果提示了μ阿片受体细胞外环中一个替代性的“作用位点”结构域。
