Basic design of beta-lactam antibiotics: penams and analogues and monocyclic beta-lactams.
Improved microbiological and chemical techniques have resulted in the development of a range of new beta-lactam antibiotics with valuable clinical properties. The work on semi-synthetic penicillins demonstrated that by alteration of the side chain in the 6-position of the penam structure it was possible to significantly affect the antibacterial activity of the compounds and their stability against degradation by acids and beta-lactamases. Esterification of the carboxyl group in the 3-position may improve the pharmacokinetic properties of the compounds whereas substitution in the bicyclic penam structure may give compounds with strong inhibitory action against beta-lactamases. Penems are available by chemical synthesis and may have potent antibacterial activity and good stability against beta-lactamases. Carbapenems can be obtained microbiologically and chemically. The latter, include compounds which have high and broad antibacterial activity as well as those which are potent inhibitors of beta-lactamases. Many of the compounds are, however, chemically rather labile and may also be degraded by a dehydropeptidase present in the kidneys. Clavulanic acid is a microbial oxapenam with modest antibacterial activity but potent inhibitory activity against beta-lactamases. Two types of monocyclic beta-lactams with antibacterial properties, the nocardicins and the monobactams, have so far been found to be produced by microorganisms. They have modest in vitro activity, but at least in case of the monobactams it has been possible to obtain compounds by chemical derivatization with high activity against Gram-negative bacteria and with high stability against beta-lactamases.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D010406:Penicillins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical; D013845:Thienamycins / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D010406:Penicillins; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; C015537:thienamycin