Evaluation of bisbenzamidines as inhibitors for matriptase-2. Issue 15 (1st August 2016)

• Record Type: Journal Article
• Authors: Beckmann, Anna-Madeleine; Gilberg, Erik; Gattner, Susanne; Huang, Tien L.; Vanden Eynde, Jean Jacques; Mayence, Annie; Bajorath, Jürgen; Stirnberg, Marit; Gütschow, Michael
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 15(2016)
• Page Start: 3741
• Page End: 3745
• Publication Date: 2016-08-01
• Subjects: Bisbenzamidines -- Matriptase-2 -- Serine proteases; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.071
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 derivative19 and the oxamide-derived bisbenzamidine1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.