Synthesis of potent and highly selective inhibitors of human tryptase.

作者信息

Slusarchyk William A, Bolton Scott A, Hartl Karen S, Huang Ming-Hsing, Jacobs Glenn, Meng Wei, Ogletree Martin L, Pi Zulan, Schumacher William A, Seiler Steven M, Sutton James C, Treuner Uwe, Zahler Robert, Zhao Guohua, Bisacchi Gregory S

机构信息

The Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA.

出版信息

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3235-8. doi: 10.1016/s0960-894x(02)00689-3.

DOI:10.1016/s0960-894x(02)00689-3

PMID:12372541

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.

摘要