Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis
Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis
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DOI：
10.1016/j.bmc.2008.04.061
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发表时间：
2008-06-01
影响因子：
3.5
通讯作者：
Houghten, Richard A.
中科院分区：
文献类型：
--
作者：
Martinez-Mayorga, Karina;Medina-Franco, Jose L.;Houghten, Richard A.
双环胍与kappa-阿片受体活性的构象衍生在我们的实验室从位置扫描合成组合文库提出了这项工作。我们提出了一个共同的生物活性构象和假定的药效特征，通过三维相似的方法。我们的“Y”形分子结合模型解释了结构-活性关系，并表明胍的功能和4-甲氧基苯基可能参与了与受体的关键相互作用。我们的模型与已知阿片类药物的比较显示了相似的结合模式，表明本研究中提出的双环胍类药物是进一步开发新的阿片受体配体的合适支架。(C) 2008 Elsevier Ltd版权所有。
Conformation of bicyclic guanidines with kappa-opioid receptor activity derived in our laboratory from a positional scanning synthetic combinatorial library is presented in this work. We propose a common bioactive conformation and putative pharmacophoric features by means of 3D similarity methods. Our 'Y' shape molecular binding model explains structure-activity relationships and suggests that the guanidine functionality and a 4-methoxybenzyl group may be involved in key interactions with the receptor. Comparison of our model with known opiates suggest a similar binding mode showing that the bicyclic guanidines presented in this work are suitable scaffolds for further development of new opioid receptors ligands. (C) 2008 Elsevier Ltd. All rights reserved.