Author/Authors :
J?rg Stürzebecher، نويسنده , , Helmut Vieweg، نويسنده , , Torsten Steinmetzer، نويسنده , , Andrea Schweinitz، نويسنده , , Christopher T. Walsh and Milton T. Stubbs، نويسنده , , Martin Renatus، نويسنده , , Peter Wikstr?m، نويسنده ,
Abstract :
Synthesis and anti-uPA activity of a series of Nα-triisopropyl-phenylsulfonyl-protected 3-amidino-phenylalanine amides are described. We have explored SAR around the C-terminal amide part for inhibition of uPA, plasmin and trypsin. Modification of the amide part has been found to affect potency but not selectivity. With a Ki of 0.41 μM 2r-L is one of the most potent uPA inhibitors described so far. The X-ray crystal structure of 2r-L was solved in complex with trypsin, superimposed with uPA and the results suggest an unique binding mode of this inhibitor type.
