Author/Authors :
Philippe G. Nantermet، نويسنده , , James C. Barrow، نويسنده , , Christina L. Newton، نويسنده , , Janetta M. Pellicore، نويسنده , , MaryBeth Young، نويسنده , , S. Dale Lewis، نويسنده , , Bobby J. Lucas Jr.، نويسنده , , Julie A. Krueger، نويسنده , , Daniel R. McMasters، نويسنده , , Youwei Yan، نويسنده , , Lawrence C. Kuo، نويسنده , , Joseph P. Vacca، نويسنده , , Harold G. Selnick، نويسنده ,
Abstract :
A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.
