The 2-pyridone antibacterial agents: 8-position modifications

Improved potency against multiply resistant streptococci and anaerobic micr oorganisms relative to current antibiotics has been sought by many laborato ries around the world. As one result of attempts to prepare analogs of 4-qu inolone anti-infectives bearing novel ring systems, the 2-pyridones were di scovered. The 2-pyridones, which are bioisosteres of 4-quinolones, are high ly active against a wide range of resistant strains of bacteria. Several hu ndreds of 2-pyridones have been synthesized incorporating modifications at various positions. In order to reduce the complexity of this review, only t he widely adopted 8-position modifications (corresponding to the 7-position of the quinolones) will be discussed here. From scientific publications an d patents, it is clear that many of the 2-pyridones are very promising cand idates and yet only selective members of these compounds have been advanced to detailed preclinical trials. Among the promising candidates, A-170568 w as demonstrated to have the best overall profile in terms of the in vitro a nd in vivo antibacterial activities, safety profile, and tissue penetration .