Bioorganic and Medicinal Chemistry Letters p. 3229 - 3233 (2002)
Update date:2022-08-04
Topics:
Sutton, James C.
Bolton, Scott A.
Hartl, Karen S.
Huang, Ming-Hsing
Jacobs, Glenn
Meng, Wei
Ogletree, Martin L.
Pi, Zulan
Schumacher, William A.
Seiler, Steven M.
Slusarchyk, William A.
Treuner, Uwe
Zahler, Robert
Zhao, Guohua
Bisacchi, Gregory S.
A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and selective tryptase inhibitor which, when dosed intratracheally in ovalbumin-sensitized guinea pigs, reduced allergen-induced bronchoconstriction and inflammatory cell infiltration into the lung.
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