4-[6-(2-Aminoethyl)naphthalen-2-yl]benzonitriles are potent histamine H3 receptor antagonists with high CNS penetration

被引：18
|
作者：
Black, Lawrence A. [1 ]
Nersesian, Diana L.
Sharma, Padam
Ku, Yi-Yin
Bennani, Youssef L.
Marsh, Kennan C.
Miller, Thomas R.
Esbenshade, Timothy A.
Hancock, Arthur A.
Cowart, Marion
机构：
[1] Abbott Labs, GPRD, Neurosci Res, Abbott Pk, IL 60064 USA
[2] Abbott Labs, GPRD, Proc Res, Abbott Pk, IL 60064 USA
[3] Abbott Labs, GPRD, Exploratory Sci, Abbott Pk, IL 60064 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期
关键词：
histamine H3 receptor antagonists; naphthalene; high CNS penetration;
D O I：
10.1016/j.bmcl.2006.11.073
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
4-[6-(2-Tertiaryaminoethyl)naphthalen-2-yl]benzonitriles are conformationally constrained histamine H-3 receptor antagonists with high potency and selectivity. The analogs were designed around a naphthalene core, with the goal of enhancing lipophilicity and CNS penetration, as compared to a previously reported benzofuran series. The SAR of the tertiary amine moiety is similar to that reported for the benzofuran series, with analogs bearing a 2-methylpyrrolidine substituent possessing the greatest rat and human H-3 receptor binding affinities. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1443 / 1446
页数：4
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