Decahydroisoquinoline derivatives as novel non-peptidic, potent and subtype-selective somatostatin sst3 receptor antagonists

被引：15

作者：

Troxler, Thomas ^{[1
]}

Hurth, Konstanze

Schuh, Karl-Heinrich

Schoeffter, Philippe ^{[1
]}

Langenegger, Daniel ^{[1
]}

Enz, Albert ^{[1
]}

Hoyer, Daniel ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Neurosci Dis Area, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期

关键词：

Somatostatin; GPCR; Somatostatin sst(3) receptor; Non-peptidic somatostatin receptor ligands; Subtype-selective sst(3) receptor antagonists; CSF SOMATOSTATIN; BRAIN; IDENTIFICATION; BINDING; GROWTH; SAR;

D O I：

10.1016/j.bmcl.2010.01.063

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from non-peptidic sst(1)-selective somatostatin receptor antagonists, first compounds with mixed sst(1)/sst(3) affinity were identified by directed structural modifications. Systematic optimization of these initial leads afforded novel, enantiomerically pure, highly potent and sst(3)-subtype selective somatostatin antagonists based on a (4S,4aS,8aR)-decahydroisoquinoline-4-carboxylic acid core moiety. These compounds can efficiently be synthesized and show promising PK properties in rodents. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1728 / 1734

页数：7

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