Semisynthetic beta-lactam antibiotics Synthesis and antibacterial activity of 6-beta- -2- -alkanecarboxyamidophenylacetamido-penicillanic acids
Tsou, T.L.; Ho, S.N.; Chang, L.R.
Chinese Pharmaceutical Journal 45(6): 563-572
ISSN/ISBN: 1016-1015 Accession: 033339439
In order to improve the antibacterial activity, a series of 6-beta-((R)-alpha-amino-phenylacetamido)penicillanic acid with various substituents at the alpha-amino group were synthesized. Structures of these products were determined by 1H-NMR, FAB-MS and FT-IR spectral analyses. In comparison with the parent drugs, compounds 4aX apprx 4dY having a diacetoxyphenylalkylcarbonyl group are active in vitro against Gram(+) and Gram(-) bacteria, including Pseudomonas aeruginosa. The others 4eX apprx 4gY displayed active only in Staphylococcus and Streptococcus strains. For the beta-lactamase producing strains, all of the derivatives are inferior to the parent drugs. The structure-activity relationships of these derivatives indicated some facts. First, compounds with increasing number of carbon atoms between the diacetoxyphenyl moiety and alpha-amino group of ampicillin or amoxicillin would retain the potency against all the tested strains. Second, compounds with increasing lipophilicity of the side chains exhibited less active against Gram(-) bacteria.