Evaluation of bisbenzamidines as inhibitors for matriptase-2

详细信息    查看全文

• 作者：Anna-Madeleine Beckmann^a ; Erik Gilberg^a ; ^b ; Susanne Gattner^a ; Tien L. Huang^c ; Jean Jacques Vanden Eynde^c ; Annie Mayence^c ; Jü ; rgen Bajorath^b ; Marit Stirnberg^a ; Michael Gü ; tschow^a ;
• 关键词：Bisbenzamidines ; Matriptase-2 ; Serine proteases
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：26
• 期：15
• 页码：3741-3745
• 全文大小：1091 K

文摘

The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.