Solid-phase synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors.
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.
Sutton
James C
JC
The Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. james.sutton@bms.com
Bolton
Scott A
SA
Davis
Malcolm E
ME
Hartl
Karen S
KS
Jacobson
Bruce
B
Mathur
Arvind
A
Ogletree
Martin L
ML
Slusarchyk
William A
WA
Zahler
Robert
R
Seiler
Steven M
SM
Bisacchi
Gregory S
GS
D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D012697:Serine Endopeptidases / Q000737:chemistry / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053802:Tryptases
C116379:2-azetidinone; D001384:Azetidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053802:Tryptases