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
  • 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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