X-ray crystal structure of the opioid ligand naltrexonazine.
X-ray crystal structure of the opioid ligand naltrexonazine.
复制标题
阿片类配体纳曲嗪的 X 射线晶体结构。
DOI：
10.1021/jm00391a035
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发表时间：
1987
影响因子：
7.3
通讯作者：
Portoghese,PS
中科院分区：
文献类型：
--
作者：
Urbanczyk-Lipkowska,Z;Lipkowski,AW;Etter,MC;Hahn,EF;Pasternak,GW;Portoghese,PS
The anti-anti isomer of naltrexonazine (1) was synthesized, and its configuration was confirmed by X-ray crys-tallography. The syn-anti isomer is readily convertedto 1 under acidic conditions. The apparent equal receptor binding of 1 and syn-anti isomer indicates that isomerization of the azine moiety may take place under the conditions of biological evaluation. Two possible explanations for wash-resistant binding of 1 to opioid receptors are presented. The first possibility involves a noncovalent interaction of the ligand with the opioidreceptor, and the second considers covalent binding by a receptor-based sulfhydryl group.Molecules that consist of two pharmacophores connected by a spacer chain have been termed bivalent ligands3-9 and are of interest as probes for opioid receptors because of the possibility of “bridging” a subpopulation of vicinal receptors when the spacer is a specific length. The binding and biological activities of bivalent ligands derived from naloxone, naltrexone, and oxymorphonein which two al-kaloid pharmacophores are connected by an azine moiety have been reported. 10-13 In this connection, the opioid receptor binding characteristics of naltrexonazine (1) and related azines to brain membranes have been investigated. On the basis of their reversible and wash-resistant binding components, Wolozin and Pasternak14 divided ต receptors into two distinct ต subtypes. The naloxonazine-selective reversible and wash-resistant properties have been sug-
