title: 6-(1-Hydroxyalkyl)penam sulfone derivatives as inhibitors of class A and class C beta-lactamases I.
abstract: 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.
authors.affiliation: Chemical Sciences and Infectious Diseases, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bitha
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: G D
authors.initials: GD
authors.lastname: Francisco
authors.forename: B A
authors.initials: BA
authors.lastname: Rasmussen
authors.forename: Y I
authors.initials: YI
authors.lastname: Lin
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D013450:Sulfones; D065093:beta-Lactamase Inhibitors