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ID: ALA1132784

Journal: Bioorg Med Chem Lett

Title: Dibasic inhibitors of human mast cell tryptase. Part 2: structure-activity relationships and requirements for potent activity.

Authors: Rice KD, Wang VR, Gangloff AR, Kuo EY, Dener JM, Newcomb WS, Young WB, Putnam D, Cregar L, Wong M, Simpson PJ.

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.

CiteXplore: 11055356

DOI: 10.1016/s0960-894x(00)00485-6