title: 6-(1-Hydroxyalkyl))penam sulfone derivatives as inhibitors of class A and class C beta-lactamases II.
abstract: Two stereoselective processes for the synthesis of novel 3,6-disubstituted penam sulfone derivatives were developed. One 6beta-(1-hydroxyethyl) and four 6beta-hydroxymethyl penam sulfone derivatives were synthesized. All four 6beta-(hydroxymethyl)penam sulfone derivatives demonstrated good IC50 against both TEM-1 and AmpC beta-lactamases. Of these, 6beta-hydroxymethyl penam sulfone derivative 25 was the most active inhibitor which was able to restore the activity of piperacillin in vitro and in vivo against both TEM-1 and AmpC beta-lactamases producing organisms.
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: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: P J
authors.initials: PJ
authors.lastname: Petersen
authors.forename: E
authors.initials: E
authors.lastname: Lenoy
authors.forename: Y I
authors.initials: YI
authors.lastname: Lin
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D012706:Serratia marcescens / Q000201:enzymology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D013450:Sulfones; D065093:beta-Lactamase Inhibitors