Syntheses of new isodethiaazacephems as potent antibacterial agents.
New isodethiaazacephems (+/-)-3, (+/-)-4, and (+/-)-10 as well as the 4-sulfonylated isodethiaazacepham (+/-)-5 were synthesized by chemical methods and found to possess biological activity against five pathogenic microorganisms in vitro. The mesylate and the triflate functionalities in (+/-)-3 and (+/-)-4, acting as effective leaving groups, enhanced remarkably the biological activity in comparison with the parent 3-hydroxyisodethiaazacephem (+/-)-10. The mode of action related to (+/-)-3 and (+/-)-4 can be explained by a [1,4]-elimination process.
Hwu
J R
JR
Organosilicon and Synthesis Laboratory, Institute of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan 11529, Republic of China.
Tsay
S C
SC
Hakimelahi
S
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D007769:Lactams; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012485:Salmonella typhi / Q000187:drug effects; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007769:Lactams