Dibasic inhibitors of human mast cell tryptase. Part 2: structure-activity relationships and requirements for potent activity |
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| Authors: | Rice K D Wang V R Gangloff A R Kuo E Y Dener J M Newcomb W S Young W B Putnam D Cregar L Wong M Simpson P J |
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| Institution: | Department of Medicinal Chemistry, Axys Pharmaceuticals, Inc., South San Francisco, CA 94080, USA. |
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| 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. |
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