Derivatives of 4-amino-pyridine as selective thrombin inhibitors

被引：29

作者：

vonderSaal, W ^{[1
]}

Kucznierz, R ^{[1
]}

Leinert, H ^{[1
]}

Engh, RA ^{[1
]}

机构：

[1] MAX PLANCK INST BIOCHEM, D-82152 MARTINSRIED, GERMANY

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(97)00210-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

During screening for novel thrombin inhibitors it was discovered that the il-aminopyridine derivative 1 inhibits human alpha-thrombin competitively and selectively. The 4-aminopyridine moiety itself is most likely the major determinant of the selectivity due to the increased hydrophobicity of the S1 pocket in thrombin compared to trypsin and plasmin. Optimization led to the selective thrombin inhibitor 14 with an inhibition constant, Ki of 70 nM. (C) 1997 Elsevier Science Ltd.

引用

页码：1283 / 1288

页数：6

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