Trypsin inhibitors for the treatment of pancreatitis

被引：15
|
作者：
Brandl, Trixi [1 ]
Simic, Oliver [1 ]
Skaanderup, Philip R. [1 ]
Namoto, Kenji [1 ]
Berst, Frederic [1 ]
Ehrhardt, Claus [1 ]
Schiering, Nikolaus [1 ]
Mueller, Irene [1 ]
Woelcke, Julian [2 ]
机构：
[1] Novartis Pharma AG, Novartis Inst BioMed Res, Novartis Campus, CH-4002 Basel, Switzerland
[2] Novartis Pharma AG, Cardio Metab Dev Franchise, Novartis Campus, CH-4002 Basel, Switzerland
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 17期
关键词：
Trypsin inhibitor; Pancreatitis; hERG inhibition; X-ray crystal structure; HEREDITARY PANCREATITIS; DISCOVERY; MUTATIONS; DIAGNOSIS; GENE;
D O I：
10.1016/j.bmcl.2016.07.029
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Proline-based trypsin inhibitors occupying the S1-S2-S1' region were identified by an HTS screening campaign. It was discovered that truncation of the P1' moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4340 / 4344
页数：5
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