7-芳基吗啡喃的合成。探究阿片δ受体选择性的“定位”要求。

Synthesis of 7-arylmorphinans. Probing the "address" requirements for selectivity at opioid delta receptors.

作者信息

Gao P, Larson D L, Portoghese P S

机构信息

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, USA.

出版信息

J Med Chem. 1998 Jul 30;41(16):3091-8. doi: 10.1021/jm9802214.

DOI:10.1021/jm9802214

PMID:9685249

Abstract

Through arylation of 6-keto opiates with diaryliodonium iodide, a series of 7-aryl opiates (3-8) have been prepared in an effort to investigate the effect of conformational mobility of the delta "address" moiety on opioid agonist and antagonist potencies. Evaluation of the ligands in the mouse vas deferens and guinea pig ileum preparations revealed that they were less potent and less selective than the conformationally constrained ligands, naltrindole (1, NTI) and 7-(spiroindanyl)oxymorphone (2, SIOM), at delta opioid receptors. It is concluded that the coplanarity of the address moiety with the C ring of the morphinan structure enhances delta antagonist potency and selectivity.

摘要

通过用二芳基碘鎓碘化物对6-酮基阿片类药物进行芳基化反应，制备了一系列7-芳基阿片类药物（3-8），旨在研究δ“识别”部分的构象流动性对阿片类激动剂和拮抗剂效力的影响。在小鼠输精管和豚鼠回肠制剂中对这些配体进行评估发现，在δ阿片受体上，它们的效力和选择性均低于构象受限的配体纳曲吲哚（1，NTI）和7-（螺茚满基）羟吗啡酮（2，SIOM）。得出的结论是，识别部分与吗啡喃结构的C环的共面性增强了δ拮抗剂的效力和选择性。