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Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors.

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Sutton JC,Bolton SA,Hartl KS,Huang MH,Jacobs G,Meng W,Ogletree ML,Pi Z,Schumacher WA,Seiler SM,Slusarchyk WA,Treuner U,Zahler R,Zhao G,Bisacchi GS

doi

10.1016/s0960-894x(02)00688-1

subject

Has Abstract

pub_date

2002-11-04 00:00:00

pages

3229-33

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960894X02006881

journal_volume

12

pub_type

杂志文章

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