title: Cladinose analogues of sixteen-membered macrolide antibiotics. IV. Improved therapeutic effects of 4-O-acyl-L-cladinose analogues of sixteen-membered macrolide antibiotics.
abstract: Six derivatives of sixteen-membered macrolides possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar were synthesized via 3"-methylthiomethyl ether intermediates in reasonable yield. Introduction of a methyl group on the 3"-hydroxyl group of midecamycin A1 was effective for enhancing its antibacterial activity. All these derivatives exhibited excellent therapeutic effects in mice, and some of them showed improved pharmacokinetics compared with the natural antibiotics (mycarose type) in mice. Facile synthesis of 9-O-acylated analogues are also described.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ajito
authors.forename: K
authors.initials: K
authors.lastname: Kurihara
authors.forename: S
authors.initials: S
authors.lastname: Shibahara
authors.forename: O
authors.initials: O
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Okonogi
authors.forename: N
authors.initials: N
authors.lastname: Kikuchi
authors.forename: M
authors.initials: M
authors.lastname: Araake
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Omoto
authors.forename: S
authors.initials: S
authors.lastname: Inouye
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004352:Drug Resistance, Microbial; D006601:Hexoses / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D011008:Pneumococcal Infections / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D006601:Hexoses; D018942:Macrolides; C013889:cladinose