Ciprofloxacin and most of the other available quinolones are fluoroquinolones with a fluorine atom at the C-6 position of the quinolone ring structure. It appeared from computer modelling studies that introducing an additional substitution at the C-8 position might increase its inhibitory action; as a result finafloxacin was synthesised.1 This molecule contains a cyano group at C-8. Invented by Bayer scientists, it is being developed by MerLion Pharmaceuticals, initially as a potential treatment for Helicobacter pylori eradication, as it is thought it will be particularly active in acidic environments such as the stomach. It should also have potential in urinary tract and gastrointestinal infections.
In a Phase I trial, healthy volunteers were given the drug as a single oral dose of 25–800mg, or repeated doses of 150–800mg for seven days. Side-effects included headache, diarrhoea, nausea, tiredness and cranial pressure.2 It was well tolerated. In another study, the highest single oral dose, 800mg, was given to six healthy individuals in a second Phase I study.3 It was shown to be active ex vivo against a variety of pathogens implicated in UTIs.
A recent in vitro study showed it retains activity against the bacterium Acinetobacter baumanii, in which resistance is a growing problem.4 It was shown to be active against ciprofloxacin-resistant strains, and its activity is enhanced under acidic conditions. Phase II trials are now under way in UTIs and H. pylori infections.
References
1. J. Hong et al. Tetrahedron Lett. 2009, 50, 2525
2. H. Patel et al. 48th Ann. Intersci. Conf. Antimicrob. Ag. Chemother. (Oct 28-28, Washington DC), 2008, Abst F1- 2048
3. F.M.E. Wagenlehner et al. 48th Ann. Intersci. Conf. Antimicrob. Ag. Chemother. (Oct 28-28, Washington DC), 2008, Abst. F1-2049
4. P.G. Higgins et al. Antimicrob. Agents Chemother 2010, 54, 1613
