title: Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 1. Newly generated antibacterial activities against Gram-positive bacteria with erm gene by C-7 modification.
abstract: We synthesized 7(S)-7-deoxy-7-arylthiolincomycin derivatives possessing a heterocyclic ring at the C-7 position via sulfur atom by either Mitsunobu reaction of 2,3,4-tris-O-(trimethylsiliyl)lincomycin or SN2 reaction of 7-O-methanesulfonyl-2,3,4-tri-O-trimethylsiliyllincomycin. As a result, 7(S)-7-deoxy-7-arylthiolincomycin derivatives 16, 21 and 27 exhibited antibacterial activities against respiratory infection-related Gram-positive bacteria with erm gene, although clindamycin did not have any activities against those pathogens. Furthermore, 7(S)-configuration of lincomycin derivatives was found to be necessary for enhancing antibacterial activities from the comparison results of configurations of 16 (S-configuration) and 30 (R-configuration) at the 7-position.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Wakiyama
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Kumura
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Umemura
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Masaki
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kumura
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fushimi
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Kohoku-ku, Yokohama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ajito
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008034:Lincomycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008780:Methyltransferases / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008034:Lincomycin; D008780:Methyltransferases; C431709:ErmA protein, Bacteria