[Synthesis and antibacterial action of new ureido- and dicarboxylic acid diamido- derivatives of acylpenicillins with and without catechol substituents].
New ureido, oxamoyl, fumaramoyl and terephthalamoyl derivatives of ampicillin or amoxicillin were synthesized by reaction of acylpenicillines with o-dihydroxy- or o-diacyloxy substituents containing aromatic amines bound over CO- or dicarboxylic groups. Corresponding compounds derived from 3,4-diacetoxyaniline showed significant increase of activity against pseudomonas and salmonella in contrast to derivatives without catechol substituents. No increase of activity was observed by corresponding derivatives of bi- and tricyclic amines. Derivatives with oxamoyl, fumaramoyl or terephthalamoyl groups were found to be more active than the corresponding ureido derivatives. Studies with mutants possessing higher membrane permeability have shown that the high activities of catechol containing derivatives are connected with the improved penetration through the outer membrane. Some new penicillin derivatives are more stable against beta-lactamases compared with azlocillin.
Heinisch
L
L
Hans-Knöll-Institut für Naturstoff-Forschung e.V., Jena.
Möllmann
U
U
Tresselt
D
D
Willitzer
H
H
D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D002396:Catechols; D010406:Penicillins; D001618:beta-Lactamases
Synthese und antibakterielle Wirkung neuer Ureido- und Dicarbonsäurediamidoderivate von Acylpenicillinen mit und ohne Catecholsubstituenten.