6-(1-Hydroxyalkyl)penam sulfone derivatives as inhibitors of class A and class C beta-lactamases I.
Five 6-(1-hydroxyalkyl)penam sulfone derivatives and two 6-(hydroxymethyl)penams were synthesized for beta-lactamase inhibitor screens. The substituent effects and stereochemical requirements of 6alpha- and 6beta-(1-hydroxyalkyl) groups for the biological activity of penam sulfone derivatives were investigated. Of these substituents, only the 6beta-hydroxymethyl group of 15 improved the activity of sulbactam against both TEM-1 and AmpC beta-lactamases. The sulfone moiety is required for the enhancement of the beta-lactamase inhibitory activity. 6Beta-hydroxymethylsulbactam (15) was able to restore the activity of piperacillin in vitro and in vivo against various beta-lactamase producing microorganisms.
Bitha
P
P
Chemical Sciences and Infectious Diseases, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
Li
Z
Z
Francisco
G D
GD
Rasmussen
B A
BA
Lin
Y I
YI
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D004791:Enzyme Inhibitors; D013450:Sulfones; D065093:beta-Lactamase Inhibitors