Studies on anti-Helicobacter pylori agents. Part 3: A novel, efficacious cephem derivative, FR193879.
The synthesis, therapeutic efficacy against H. pylori, and preliminary safety of the novel cephem derivative, FR193879 (8a) are described. Compound 8a having a (4-carbamoylmethylthiazol-2-yl)thio moiety at the 3-position and a phenylacetamido at the 7-position was found to have good safety showing a nontoxic dose of > 100 mg/kg in dogs in a 4-week repeat dose toxicity study and extremely potent therapeutic efficacy against H. pylori, showing 30 times superior activity compared to AMPC, and did not display cross-resistance with CAM or MNZ.
Yoshida
Yoshiki
Y
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. yoshiki_yoshida@po.fujisawa.co.jp
Matsuda
Keiji
K
Sasaki
Hiroshi
H
Matsumoto
Yoshimi
Y
Matsumoto
Satoru
S
Tawara
Shuichi
S
Takasugi
Hisashi
H
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002511:Cephalosporins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D004355:Drug Stability; D006168:Guinea Pigs; D016480:Helicobacter pylori / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D010599:Pharmacokinetics; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D016896:Treatment Outcome
D000081:Acetamides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C494039:FR193879; D013844:Thiazoles