title: Synthesis and antibacterial activity of 6-O-(heteroaryl-isoxazolyl)propynyl 2-fluoro ketolides.
abstract: Macrolide antibiotics are widely prescribed for the treatment of respiratory tract infections; however, the increasing prevalence of macrolide-resistant pathogens is a public health concern. Therefore, the development of new macrolide derivatives with activities against resistant pathogens is urgently needed. A series of novel 6-O-(heteroaryl-isoxazolyl)propynyl 2-fluoro ketolides has been synthesized from erythromycin A. These compounds have shown very promising in vitro and in vivo antibacterial activities against key respiratory pathogens including erythromycin-susceptible/resistant strains.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. tomohiro.sugimoto@po.rd.taisho.co.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Manaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanikawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kayoko
authors.initials: K
authors.lastname: Nanaumi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006192:Haemophilus Infections / Q000188:drug therapy; D006193:Haemophilus influenzae / Q000187:drug effects*; D054879:Halogenation; D006801:Humans; D048628:Ketolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013210:Staphylococcus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D004917:Erythromycin