Piperidinyl-nicotinamides as potent and selective somatostatin receptor subtype 5 antagonists

被引：11

作者：

Alker, Andre ^{[2
]}

Binggeli, Alfred ^{[1
]}

Christ, Andreas D. ^{[3
]}

Green, Luke ^{[1
]}

Maerki, Hans Peter ^{[1
]}

Martin, Rainer E. ^{[1
]}

Mohr, Peter ^{[1
]}

机构：

[1] F Hoffmann La Roche Ltd, Div Pharmaceut, Med Chem, CH-4070 Basel, Switzerland

[2] F Hoffmann La Roche Ltd, Div Pharmaceut, Mol Struct Res, CH-4070 Basel, Switzerland

[3] F Hoffmann La Roche Ltd, Div Pharmaceut, Discovery Metab & Vasc Dis, CH-4070 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

GPCR; Somatostatin; Pancreas; Antagonists; EXPRESSION; CELLS; DISCOVERY; SECRETION; PANCREAS;

D O I：

10.1016/j.bmcl.2010.06.026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nicotinamides of benzyl-substituted 4-aminopiperidines and their seven-membered analogs of generic structure 2 and 20 have been discovered as potent and selective SST5 antagonists. The activity (K-i) ranges from 2.4 to 436 nM. Most compounds exhibit decent physicochemical properties and follow a clear SAR pattern. Interestingly enough, the receptor is strongly enantiodiscriminating and binds in the amino-azepaneseries only the (R)-enantiomer. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4521 / 4525

页数：5

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