20299-36-9Relevant articles and documents
Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology
Nitsche, Christoph,Zhang, Linlin,Weigel, Lena F.,Schilz, Jonas,Graf, Dominik,Bartenschlager, Ralf,Hilgenfeld, Rolf,Klein, Christian D.
supporting information, p. 511 - 516 (2017/04/27)
A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range
Development of new cyclic plasmin inhibitors with excellent potency and selectivity
Saupe, Sebastian M.,Leubner, Stephanie,Betz, Michael,Klebe, Gerhard,Steinmetzer, Torsten
supporting information, p. 820 - 831 (2013/03/28)
The trypsin-like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss. The optimization of our recently described substrate-analogue plasmin inhibitors, which were cyclized between their P3 and P2 side chains, provided a new series with improved efficacy and excellent selectivity. The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0.2 nM, whereas Ki values >1 μM were determined for nearly all other tested trypsin-like serine proteases, with the exception of trypsin, which is also inhibited in the nanomolar range. Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors. The dialkylated piperazine-linker segment contributes to an excellent solubility of all analogues. Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs.
