title: FR290581, a novel sordarin derivative: synthesis and antifungal activity.
abstract: Sordarin is a unique natural product antifungal agent that is an inhibitor of elongation factor 2. To improve biological activity, we synthesized various compounds by novel modification of the aglycone, sordaricin. As a result, we have discovered the novel sordarin derivative FR290581. This compound exhibited superior activity and a good pharmacokinetic profile, and also displayed good in vivo activity against Candida albicans.
authors.affiliation: Chemistry Research Labs., Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Hanadate
authors.forename: Masaki
authors.initials: M
authors.lastname: Tomishima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morikawa
authors.forename: David
authors.initials: D
authors.lastname: Barrett
authors.forename: Satoru
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ohtomo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Maki
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D007192:Indenes / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; C543156:FR290581; D007192:Indenes; D011500:Protein Synthesis Inhibitors; C003329:sordarin