Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues.
Cephalosporins with new catechol substituents at C-3' have been synthesized, including novel compounds with C-3' carbon-carbon bonds. Many of these compounds have high potency against Gram-negative bacteria, in particular against resistant strains like Pseudomonas aeruginosa. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-3' catechol and also in terms of steric and conformational factors of the C-3' substituent. The best overall properties were found in compounds with a bulky and/or conformationally restricted acidic C-3' catechol.
Arnould
J C
JC
ICI Pharma, Centre de Recherches, Reims, France.
Bertrandie
A
A
Bird
T G
TG
Boucherot
D
D
Jung
F
F
Lohmann
J J
JJ
Olivier
A
A
Bailey
J P
JP
Bell
W
W
Davies
G M
GM
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002144:Callithrix; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004795:Enzyme Stability; D005260:Female; D008297:Male; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D001798:Blood Proteins; D002396:Catechols; D002511:Cephalosporins; D001618:beta-Lactamases