Identification and SAR of potent and selective non-peptide obeline somatostatin sst1 receptor antagonists

被引:7
|
作者
Troxler, Thomas [1 ]
Hoyer, Daniel [1 ]
Langenegger, Daniel [1 ]
Neumann, Peter [1 ]
Pfaeffli, Paul [1 ]
Sehoeffter, Philippe [1 ]
Sorg, Dieter [1 ]
Swoboda, Robert [1 ]
Hurth, Konstanze [1 ]
机构
[1] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
关键词
somatostatin sst(1) receptor antagonists; octa-hydrobenzo[g]quinolines (obelines);
D O I
10.1016/j.bmcl.2007.04.086
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A novel class of non-peptide somatostatin receptor ligands bearing the octahydrobenzo[g]quinoline (obeline) structural element has been identified. SAR studies have been performed that led to the discovery of derivatives with high affinity (pK(d) r sst(I) >= 9) and selectivity (>= 150-fold for h sst(1) over h sst(2)-h sst(5)) for somatostatin receptor subtype sst(1). In a functional assay, the compounds act as antagonists at human recombinant sst, receptors. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3983 / 3987
页数:5
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