Diarylsulfonamides as selective, non-peptidic thrombin inhibitors

被引：16
|
作者：
Weber, IR
Neidlein, R
von der Saal, W
Grams, F
Leinert, H
Strein, K
Engh, RA
Kucznierz, R [1 ]
机构：
[1] Boehringer Mannheim GmbH, Dept Chem, D-68305 Mannheim, Germany
[2] Univ Heidelberg, Inst Pharmaceut Chem, D-69120 Heidelberg, Germany
[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 13期
关键词：
D O I：
10.1016/S0960-894X(98)00269-8
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Based on the structures of aminopyridine thrombin inhibitors (1), a series of aminoalkyl- and guanidinoalkyl-substituted diarylsulfonamides were prepared. The most potent derivative, N-[3-(4-guanidinobutoxy)-5-methyl-phenyl]-benzenesulfonamide (6c) had Ki = 0.18 mu M for thrombin and did not inhibit trypsin, plasmin, or factor Xa. Comparison of the X-ray structures of the thrombin / 1b and the thrombin / 6c complexes revealed important aspects which govern the binding of such diarylsulfonamides to thrombin. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：1613 / 1618
页数：6
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