New aminothiazolylglycylcephalosporins with a 1,5-dihydroxy-4-pyridone-2-carbonyl group. I. Synthesis and biological activity of cephalosporin derivatives leading to MT0703.
A series of new aminothiazolylglycylcephalosporins with a mono- or dihydroxypyridonecarbonyl group at the alpha-amino group of the C-7 substituent have been prepared and antibacterial activity of these compounds was investigated. Among them, the compounds having a 1,5-dihydroxy-4-pyridone-2-carbonyl group showed excellent anti-pseudomonal activity. In particular, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4- pyridone-2-carboxamido)- acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4-yl]thiomethyl]ceph-3 -em- 4-carboxylate (MT0703, 7g) was found to be a well balanced compound with respect to antibacterial activity.
Ogino
H
H
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Iwamatsu
K
K
Katano
K
K
Nakabayashi
S
S
Yoshida
T
T
Tsuruoka
T
T
Inouye
S
S
Kondo
S
S
D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004927:Escherichia coli Infections / Q000188:drug therapy; D007710:Klebsiella Infections / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D002511:Cephalosporins; C063437:MT 0703