Synthesis, nicotinic acetylcholine receptor binding, and pharmacological properties of 3′-(substituted phenyl)deschloroepibatidine analogs

被引：16

作者：

Carroll, F. Ivy ^{[1
]}

Yokota, Yasuno ^{[1
]}

Ma, Wei ^{[1
]}

Lee, Jeffrey R. ^{[1
]}

Brieaddy, Lawrence E. ^{[1
]}

Burgess, Jason P. ^{[1
]}

Navarro, Hernan A. ^{[1
]}

Damaj, M. I. ^{[2
]}

Martin, Billy R. ^{[2
]}

机构：

[1] Res Triangle Inst, Res Triangle Pk, NC 27709 USA

[2] Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 02期

关键词：

D O I：

10.1016/j.bmc.2007.10.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 3'-(substituted phenyl)deschloroepibatidine analogs (5a-j) were synthesized. The alpha 4 beta 2* and alpha 7 nicotinic acetylcholine receptor (nAChR) binding properties and functional activity in the tail-flick, hot-plate, locomotor, and body temperature tests in mice of 5a-j were compared to those of the nAChR agonist, nicotine (1), epibatidine (4), and deschloroepibatidine (13), the partial agonist, varenicline (3), and the antagonist 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogs (7a-j). Unlike epibatidine and deschloroepibatidine, which are potent agonists in the tail-flick test, 5a-k show no or very low antinociceptive activity in the tail-flick or hot-plate test. However, they are potent antagonists in nicotine-induced antinociception in the tail-flick test, but weaker than the corresponding 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines. (c) 2007 Elsevier Ltd. All rights reserved.

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收藏

页码：746 / 754

页数：9

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