title: Synthesis and structure-activity relationship of a novel class of 15-membered macrolide antibiotics known as '11a-azalides'.
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 scaffolds with activities against resistant pathogens is urgently needed. An efficient method for reconstructing the erythromycin A macrolactone skeleton has been established. Based on this methodology, novel 15-membered macrolides, known as '11a-azalides', with substituents at the C12, C13, or C4″ positions were synthesized and their antibacterial activities were evaluated. These derivatives showed promising antibacterial activities against erythromycin-resistant Streptococcus pneumoniae. Among them, the C4″ substituted derivatives had the most potent activity against erythromycin-resistant S. pneumoniae.
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: Tetsuya
authors.initials: T
authors.lastname: Tanikawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D004917:Erythromycin