title: Synthesis and evaluation of N-substituted 1,4-oxazepanyl Sordaricins as selective fungal EF-2 inhibitors.
abstract: Sordaricin analogues possessing 6-methoxy-7-methyl-1,4-oxazepane moiety instead of the sugar part were synthesized and evaluated. It was found that N-substituents on the oxazepane ring had influence on biological activity. In particular, N-(2-methylpropenyl) derivative 12p exhibited potent in vitro antifungal activity. Furthermore, 12p maintained significant activity (MIC 0.25 microg/mL) against Candida albicans SANK51486 even in the presence of 20% horse serum.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. skanek@shina.sankyo.co.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Kaneko
authors.forename: Masami
authors.initials: M
authors.lastname: Arai
authors.forename: Takuya
authors.initials: T
authors.lastname: Uchida
authors.forename: Tamako
authors.initials: T
authors.lastname: Harasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Konosu
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000145:classification / Q000187:drug effects / Q000254:growth & development; D004224:Diterpenes; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D020652:Peptide Elongation Factor 2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D004224:Diterpenes; D020652:Peptide Elongation Factor 2; C116705:sordaricin