beta-lactam antibiotics. II. Structure-activity relationships of 6-[alpha-(alpha'-ureido-acylamino) acylamino] penicillanic acids.
The influence on the structure-activity relationships (S.A.R.) of the stereochemistry and various alkyl, aryl, aralkyl and heterocyclic substituents at the two chiral centres in the dipeptide side-chain of a new series of penicillins was examined. In many cases the effects of these changes had a pronounced influence on the degree of activity against Gram-positive and especially Gram-negative bacteria. Several compounds indicated that the size, shape and spatial disposition of a substituent were the parameters of importance in influencing activity, rather than it lipophilic or electronic character. The most active homologues in the series provided broad-spectrum penicillins which in terms of their in vitro antibacterial properties showed improvements over certain of the marketed penicillins. Thus 6-[D-alpha(alpha'-ureidoacyl-amino)acylamino]penicillanic acids were found which had a carbenicillin-like profile, with improvements against Pseudomonas aeruginosa, Klebsiella aerogenes, sensitive and beta-lactamase-producing Gram-positive cocci.
D001419:Bacteria / Q000187:drug effects; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D008968:Molecular Conformation; D010406:Penicillins / Q000138:chemical synthesis / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D010406:Penicillins