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

页码：1443 / 1446

页数：4

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