Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 8. High affinity ligands for opioid receptors in the picomolar Ki range: Oxygenated N-(2-[1,1′-biphenyl]-4-ylethyl) analogues of 8-CAC

被引：6

作者：

Wentland, Mark P. ^{[1
]}

Jo, Sunjin ^{[1
]}

Gargano, Joseph M. ^{[1
]}

VanAlstine, Melissa A. ^{[1
]}

Cohen, Dana J. ^{[2
]}

Bidlack, Jean M. ^{[2
]}

机构：

[1] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Troy, NY 12180 USA

[2] Univ Rochester, Sch Med & Dent, Dept Pharmacol & Physiol, Rochester, NY 14642 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 24期

关键词：

Opioid ligands; Carboxamide; BINDING PROPERTIES; 8-CARBOXAMIDOCYCLAZOCINE; CYCLAZOCINE; COCAINE;

D O I：

10.1016/j.bmcl.2012.10.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-[2-(4'-methoxy[1,1'-biphenyl]-4-yl) ethyl]-8-CAC (1) is a high affinity (K-i = 0.084 nM) ligand for the mu opioid receptor and served as the lead compound for this study. Analogues of 1 were made in hopes of identifying an SAR within a series of oxygenated (distal) phenyl derivatives. A number of new analogues were made having single-digit pM affinity for the l receptor. The most potent was the 3',4'-methylenedioxy analogue 18 (K-i = 1.6 pM). (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7340 / 7344

页数：5

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