Author/Authors :
Kenneth D. Rice، نويسنده , , Vivian R. Wang، نويسنده , , Anthony R. Gangloff، نويسنده , , Elaine Y. -L. Kuo، نويسنده , , Jeffrey M. Dener، نويسنده , , William S. Newcomb، نويسنده , , Wendy B. Young، نويسنده , , Daun Putnam، نويسنده , , Lynne Cregar، نويسنده , , Martin Wong، نويسنده , , Paul J. Simpson، نويسنده ,
Abstract :
Detailed structure–activity relationships (SARs) for a series of dibasic human tryptase inhibitors are presented. The structural requirements for potent inhibitory activity are remarkably broad with a range of core template modifications being well tolerated. Optimized inhibitors demonstrate potent anti-asthmatic activity in a sheep model of allergic asthma. APC-2059, a dibasic tryptase inhibitor with subnanomolar activity, has been advanced to phase II clinical trials for the treatment of both psoriasis and ulcerative colitis.
