Discovery of the first N-substituted 4β-methyl-5-(3-hydroxyphenyl) morphan to possess highly potent and selective opioid δ receptor antagonist activity

被引：16
|
作者：
Carroll, FI
Zhang, L
Mascarella, SW
Navarro, HA
Rothman, RB
Cantrell, BE
Zimmerman, DM
Thomas, JB
机构：
[1] Res Triangle Inst, Res Triangle Pk, NC 27709 USA
[2] NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA
[3] Eli Lilly & Co, Lilly Res Lab, Lilly Corp Ctr, Indianapolis, IN 46285 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 02期
关键词：
D O I：
10.1021/jm030419a
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A structurally novel opioid 6 receptor selective antagonist has been identified. This compound, (+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]-non-7-yl-(1- phenyl-1-cyclopentane)carboxamide [(+)-KF4, (+)4], showed a K-e value of 0.15 nM in the [S-35]GTPgammaS functional assay. (+)-KF4 is also a 6 inverse agonist with an IC50 value of 1.8 nM. To our knowledge, this is the first potent and selective 6 opioid receptor antagonist from the 5-phenylmorphan class of opioids.
引用
收藏
页码：281 / 284
页数：4
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