Allyl and propargyl substituted penam sulfones as versatile intermediates toward the syntheses of new beta-lactamase inhibitors.
Several alkenyl derivatives were prepared using allyl penam sulfone as the key intermediate. Isomers of these derivatives having beta configuration at C-6 showed potent activity against CcrA enzyme. A new method was developed to prepare propargyl penam sulfone. The majority of the triazoles prepared by this route exhibited good activity against all three representative enzymes used for the inhibition assay.
Sandanayaka
V P
VP
Chemical Sciences and Infectious Diseases, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. sandanv@war.wyeth.com
Feigelson
G B
GB
Prashad
A S
AS
Yang
Y
Y
Petersen
P J
PJ
D000475:Alkenes / Q000138:chemical synthesis; D000480:Alkynes / Q000138:chemical synthesis; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004926:Escherichia coli; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology*; D000078142:Tazobactam; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases
D000475:Alkenes; D000480:Alkynes; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D013450:Sulfones; D014230:Triazoles; D065093:beta-Lactamase Inhibitors; C022030:methylacetylene; D010397:Penicillanic Acid; C013658:propylene; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; C063912:carbapenemase; D000078142:Tazobactam