title: RU-79115 (Aventis Pharma).
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].
authors.affiliation: Faculty of Pharmacy, University of Toronto, ON, Canada.
authors.forename: S C
authors.initials: SC
authors.lastname: Annedi
authors.forename: L P
authors.initials: LP
authors.lastname: Kotra
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003374:Coumarins / Q000493:pharmacokinetics / Q000494:pharmacology*; D016983:Enterococcus / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006601:Hexoses / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D010330:Patents as Topic; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D006601:Hexoses; C416353:RU 79115; D059005:Topoisomerase II Inhibitors