Studies on anti-Helicobacter pylori agents. Part 2: new cephem derivatives.
The synthesis and optimization of the anti-Helicobacter pylori activity of a novel series of cephem derivatives are described. Introduction of thio-heterocyclic groups containing N- and S-atoms to the 3-position and phenyl or thienyl acetamido groups to the 7-position of the cephem nucleus dramatically improved the activity. From this series of derivatives, compound 13i was found to have extremely potent in vitro anti-H. pylori activity, superior therapeutic efficacy compared to AMPC and CAM, no cross-resistance between CAM or MNZ and low potential for causing diarrhea due to instability to beta-lactamase.
Yoshida
Y
Y
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. yoshiki_yoshida@po.fujisawa.co.jp
Matsuda
K
K
Sasaki
H
H
Matsumoto
Y
Y
Matsumoto
S
S
Tawara
S
S
Takasugi
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology*; D003967:Diarrhea / Q000139:chemically induced; D004355:Drug Stability; D005753:Gastric Mucosa / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D006571:Heterocyclic Compounds; D001618:beta-Lactamases