Design, synthesis and SAR of a novel series of benzimidazoles as potent NPY Y5 antagonists

被引：5

作者：

Pizzi, Domenica Antonia ^{[1
]}

Leslie, Colin Philip ^{[1
]}

Mazzali, Angelica ^{[1
]}

Seri, Catia ^{[1
]}

Biagetti, Matteo ^{[1
]}

Bentley, Jonathan ^{[1
]}

Genski, Thorsten ^{[1
]}

Di Fabio, Romano ^{[1
]}

Contini, Stefania ^{[1
]}

Sabbatini, Fabio Maria ^{[1
]}

Zonzini, Laura ^{[1
]}

Caberlotto, Laura ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Neurosci Ctr Excellence Drug Discovery, Med Res Ctr, I-37135 Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 23期

关键词：

NPY Y5; Benzimidazoles; NEUROPEPTIDE-Y; RECEPTOR; MECHANISMS; OBESITY;

D O I：

10.1016/j.bmcl.2010.09.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of benzimidazole NPY Y5 receptor antagonists was prepared exploiting a privileged spirocarbamate moiety. The structure-activity relationship of this series and efforts to achieve a profile suitable for further development and an appropriate pharmacokinetic profile in rat are described. Optimisation led to the identification of the brain penetrant, orally bioavailable Y5 antagonist 9b which significantly inhibited the food intake induced by a Y5 selective agonist with a minimal effective dose of 30 mg/kg po. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7120 / 7123

页数：4

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