2. Academic Validation
  3. Synthesis of potent and highly selective inhibitors of human tryptase

Synthesis of potent and highly selective inhibitors of human tryptase

  • Bioorg Med Chem Lett. 2002 Nov 4;12(21):3235-8. doi: 10.1016/s0960-894x(02)00689-3.
William A Slusarchyk 1,  Scott A Bolton,  Karen S Hartl,  Ming-Hsing Huang,  Glenn Jacobs,  Wei Meng,  Martin L Ogletree,  Zulan Pi,  William A Schumacher,  Steven M Seiler,  James C Sutton,  Uwe Treuner,  Robert Zahler,  Guohua Zhao,  Gregory S Bisacchi
Affiliations

Affiliation

  • 1 The Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 12372541 DOI: 10.1016/s0960-894x(02)00689-3
Abstract

The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC(50)<1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin.

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