Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic
Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic
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DOI：
10.1016/j.ejmech.2010.12.001
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发表时间：
2011-02-01
影响因子：
6.7
通讯作者：
Neumeyer, John L.
中科院分区：
文献类型：
--
作者：
Balboni, Gianfranco;Salvadori, Severo;Neumeyer, John L.
合成了在吗啡和 δ 选择性药效团 Dmt-Tic 之间含有酯键的双功能配体，并测定了它们对 mu、δ 和 kappa 阿片受体的结合亲和力和功能生物活性。两个药效基团之间包含或不包含 β-丙氨酸间隔基的双功能配体失去源自吗啡的 mu 激动作用，成为部分 p 激动剂 mu 或 mu 拮抗剂 5。仅化合物 4 证明了部分 κ 激动作用。最后，两种化合物均显示出有效的 δ 拮抗作用。 (C) 2010 Elsevier Masson SAS。版权所有。
Bifunctional ligands containing an ester linkage between morphine and the delta-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the mu, delta and kappa opioid receptors determined. Bifunctional ligands containing or not a spacer of beta-alanine between the two pharmacophores lose the mu agonism deriving from morphine becoming partial p agonists mu or mu antagonists 5. Partial kappa agonism is evidenced only for compound 4. Finally, both compounds showed potent delta antagonism. (C) 2010 Elsevier Masson SAS. All rights reserved.