Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors.
作者信息
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
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):3229-33. doi: 10.1016/s0960-894x(02)00688-1.
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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