Quinolone prodrugs

Sanchez, J. R, Domagala, J. M., Heifetz, C. L., Priebe, S. R., Sesnie, J. A., Trehan, A. K. Quinolone antibacterial agents. Synthesis and structure—activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-l-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity. J. Med. Chem. 1992, 35, 1764-1773. 

Phosphinic Acids as Antibiotics or for Parasitic Diseases 6.1 Phosphonophosphinic Acid Quinolone Prodrugs... 

In contrast to other classes of antibiotics (aminoglucosides, P-lactams.. . ), most quinolones are well absorbed orally and only moderate efforts have been devoted to the design of prodrugs. All the reported chemistry was carried out by the team of Kanebo who tried to improve blood level and urinary recovery of norfloxacin [91, 92, 94, 95]. Compound 37, a N-masked norfloxacine prodrug liberated in vivo a high concentration of the parent compound after oral administration. In contrast, norfloxacin esters were poorly absorbed orally (Fig. 35). 

Synthesis and antimicrobial activity of 3-formyl analogs of norfloxacin, ciprofloxacin, and pefloxacin have been reported [93]. These studies have shown definitive evidence that the 3-formyl analogs of quinolones function as prodrugs and are oxidized in vivo to carboxylic acids. The higher bioavailability of formyl derivatives may be due to a change in physical and chemical properties by the lack of their amphoteric nature, compared to the parent zwitterionic compounds. 

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