(Arylpiperazinyl)cyclohexylsufonamides:: Discovery of α1a/1d-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS)

被引：9

作者：

Chiu, George ^{[1
]}

Li, Shengjian ^{[1
]}

Connolly, Peter J. ^{[1
]}

Pulito, Virginia ^{[1
]}

Liu, Jingchun ^{[1
]}

Middleton, Steven A. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ 08869 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 12期

关键词：

BPH/LUTS; alpha(1)-adrenergic receptors; alpha(1a/1d) subtype selective antagonist; (arylpiperazinyl)cyclohexylsulfonamides;

D O I：

10.1016/j.bmcl.2007.04.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1), blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a), and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3292 / 3297

页数：6

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