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
收藏
页码：1728 / 1734
页数：7
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