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

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2361-6. doi: 10.1016/s0960-894x(00)00485-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / chemical synthesis
  • Anti-Asthmatic Agents / chemistry
  • Anti-Asthmatic Agents / pharmacology
  • Asthma / drug therapy
  • Diamines / chemical synthesis*
  • Diamines / chemistry
  • Diamines / pharmacology
  • Disease Models, Animal
  • Humans
  • Kinetics
  • Molecular Structure
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Sheep
  • Structure-Activity Relationship
  • Tryptases


  • Anti-Asthmatic Agents
  • Diamines
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • Tryptases