ABSTRACT
Aventis Pharma AG is investigating a series of novel coumarin DNA gyrase B inhibitors, including RU-79115, as potential treatments for bacterial infections. These inhibitors have displayed potent inhibitory activity in vitro against DNA supercoiling by DNA gyrase B and have antibacterial activity. Good antibacterial activity against vancomycin- and teicoplanin-resistant enterococci was observed with most analogs (where the 3-acylamino residue was replaced with reversed isosteres). Amide derivatives were also active against novobiocin-resistant strains [335149]. RU-79115 has shown activity against Gram-positive bacteria, particularly staphylococci and enterococci, and its activity compares favorably to vancomycin. Against oxacillin- and ofloxacin-resistant staphylococci, RU-79115 had MIC50 values 7.5-fold lower than eperezolid and significantly lower than vancomycin. In vivo data suggest that the compound is safe and carries a satisfactory pharmacokinetic profile [216256], [340969], [376199]. The compound is the most potent in the series which also includes RU-78535 and RU-64135 [340969], [341039].
