Bioorganic and Medicinal Chemistry Letters p. 3235 - 3238 (2002)
Update date:2022-08-02
Topics:
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.
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 (IC50<1.7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin.
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