Role of the spacer in conferring kappa opioid receptor selectivity to bivalent ligands related to norbinaltorphimine.
Role of the spacer in conferring kappa opioid receptor selectivity to bivalent ligands related to norbinaltorphimine.
复制标题
间隔基在赋予 kappa 阿片受体对与降巴纳托菲明相关的二价配体选择性中的作用。
DOI：
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发表时间：
1991
影响因子：
7.3
通讯作者：
A. Takemori
中科院分区：
文献类型：
--
作者：
P. Portoghese;A. Garzon;H. Nagase;C. E. Lin;A. Takemori
The thiophene 2 and pyran 3 analogues of the kappa-selective opioid antagonist norbinaltorphimine (1a, norBNI) were synthesized and tested in an effort to determine the contribution of the spacer to the interaction of bivalent ligands at different opioid receptor types. Both 2 and 3 were found to be selective kappa opioid receptor antagonists in smooth muscle preparations, and they bound selectively to kappa-recognition sites. The thiophene analogue 2 displayed binding selectivity that was of the same order of magnitude as that of 1a, while 3 was considerably less selective for kappa site. This is consistent with the fact that the second pharmacophore in 1a and 2 displayed a greater degree of superposition than 1a and 3. The results of this study suggest that the pyrrole moiety of norBNI functions primarily as an inert spacer to rigidly hold the basic nitrogen in the second pharmacophore at an "address" subsite that is unique for the kappa opioid receptor.
