Synthesis and structure-activity relationships of a new series of cephalosporins, E1040 and related compounds.
The synthesis and in vitro antibacterial activity of a series of 7-[(Z)-2-aminoaryl-2-oxyiminoacetamido]-3-ammoniomethyl++ +-3-cephems are described. Variation of an oxyimino moiety with aminoaryl at the C-7 side chain and a quaternary ammonium moiety at the C-3 side chain were examined and structure-activity relationships were studied. E1040, the 3-(4-carbamoylquinuclidinio)methyl derivative of the 7-alpha-methoxyimino series of aminothiadiazolyl cephalosporins, exhibited excellent activity against both Gram-positive and Gram-negative bacteria, particularly against Pseudomonas aeruginosa, and possessed high stability to beta-lactamases.
Sugiyama
I
I
Tsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Komatsu
Y
Y
Yamauchi
H
H
D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013499:Surface Properties
D002511:Cephalosporins; C056494:cefclidin