A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

Abstract Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia–reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a , thrombin, and plasmin.