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ID: ALA1139445

Journal: Bioorg Med Chem Lett

Title: Synthesis of potent and selective 2-azepanone inhibitors of human tryptase.

Authors: Zhao G, Bolton SA, Kwon C, Hartl KS, Seiler SM, Slusarchyk WA, Sutton JC, Bisacchi GS.

Abstract: The serine protease tryptase has been associated with a broad range of allergic and inflammatory diseases and, in particular, has been implicated as a critical mediator of asthma. The inhibition of tryptase therefore has the potential to be a valuable therapy for asthma. The synthesis, employing solution phase parallel methods, and SAR of a series of novel 2-azepanone tryptase inhibitors are presented. A member of this series, 8t, was identified as a potent inhibitor of human tryptase (IC(50)=38 nM) with selectivity >/=330-fold versus related serine proteases (trypsin, plasmin, uPA, tPA, APC, alpha-thrombin, and FXa) [corrected].

CiteXplore: 14698147

DOI: 10.1016/j.bmcl.2003.11.016