6-(1-Hydroxyalkyl))penam sulfone derivatives as inhibitors of class A and class C beta-lactamases II.
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.
Bitha
P
P
Chemical Sciences and Infectious Diseases, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
Li
Z
Z
Francisco
G D
GD
Yang
Y
Y
Petersen
P J
PJ
Lenoy
E
E
Lin
Y I
YI
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
D004791:Enzyme Inhibitors; D013450:Sulfones; D065093:beta-Lactamase Inhibitors