Author/Authors :
Nalin L. Subasinghe، نويسنده , , Jeremy M. Travins، نويسنده , , Farah Ali، نويسنده , , Hui Huang، نويسنده , , Shelley K. Ballentine، نويسنده , , Juan Jose Marugan، نويسنده , , Ehab Khalil، نويسنده , , Heather R. Hufnagel، نويسنده , , Roger F. Bone، نويسنده , , Renee L. DesJarlais، نويسنده , , Carl S. Crysler، نويسنده , , Nisha Ninan، نويسنده , , Maxwell D. Cummings، نويسنده , , Christopher J. Molloy، نويسنده , , Bruce E. Tomczuk، نويسنده ,
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 Ki of 10 nM and >1000-fold selectivity over uPA, tPA, FXa, thrombin, and plasmin.
Keywords :
Classical pathway , complement , Complement inhibitor , C1s , C1s inhibitor , Classical pathway inhibitor
