Solid-phase synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors

James C Sutton; Scott A Bolton; Malcolm E Davis; Karen S Hartl; Bruce Jacobson; Arvind Mathur; Martin L Ogletree; William A Slusarchyk; Robert Zahler; Steven M Seiler; Gregory S Bisacchi

doi:10.1016/j.bmcl.2004.02.012

Solid-phase synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors

Bioorg Med Chem Lett. 2004 May 3;14(9):2233-9. doi: 10.1016/j.bmcl.2004.02.012.

Authors

James C Sutton¹, Scott A Bolton, Malcolm E Davis, Karen S Hartl, Bruce Jacobson, Arvind Mathur, Martin L Ogletree, William A Slusarchyk, Robert Zahler, Steven M Seiler, Gregory S Bisacchi

Affiliation

¹ The Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]

PMID: 15081015
DOI: 10.1016/j.bmcl.2004.02.012

Abstract

A series of nonguanidine N1-activated C4-carboxy azetidinone tryptase inhibitors was prepared by solid-phase methodology to quickly assess the SAR associated with distal functionality on the N1-activating group. From these studies, potent inhibitors with improved specificity were discovered.

MeSH terms

Azetidines / chemical synthesis*
Azetidines / chemistry
Azetidines / pharmacology*
Crystallography, X-Ray
Models, Molecular
Serine Endopeptidases / chemistry
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology*
Structure-Activity Relationship
Tryptases

Substances

2-azetidinone
Azetidines
Serine Proteinase Inhibitors
Serine Endopeptidases
Tryptases