Marvin Korff, Lukas Imberg, Jonas M Will, Nico Bückreiß, Svetlana A Kalinina, Benjamin M Wenzel, Gregor A Kastner, Constantin G Daniliuc, Maximilian Barth, Ruzanna A Ovsepyan, Kirill R Butov, Hans-Ulrich Humpf, Matthias Lehr, Mikhail A Panteleev, Antti Poso, Uwe Karst, Torsten Steinmetzer, Gerd Bendas, Dmitrii V Kalinin
We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i , a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound 21m with 27 nM inhibitory activity toward thrombin. For the first time, acylated 1,2,4-triazol-5-amines were proved to have anticoagulant properties and the ability to affect thrombin- and cancer-cell-induced platelet aggregation...
October 22, 2020: Journal of Medicinal Chemistry