title: Enantioselective synthesis of derivatives and structure-activity relationship study in the development of NA255 as a novel host-targeting anti-HCV agent.
abstract: Hepatitis C virus (HCV) infection represents a serious health-care problem. Previously we reported the identification of NA255 from our natural products library using a HCV sub-genomic replicon cell culture system. Herein, we report how the absolute stereochemistry of NA255 was determined and an enantioselective synthetic method for NA255 derivatives was developed. The structure-activity relationship of the NA255 derivatives and rat pharmacokinetic profiles of the representative compounds are disclosed.
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. Electronic address: kawasakikni@chugai-pharm.co.jp.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Miyako
authors.initials: M
authors.lastname: Masubuchi
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Hayase
authors.forename: Susumu
authors.initials: S
authors.lastname: Komiyama
authors.forename: Fumio
authors.initials: F
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Kouhei
authors.initials: K
authors.lastname: Koyama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shindoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Kohichi
authors.initials: K
authors.lastname: Okamato
authors.forename: Atsunori
authors.initials: A
authors.lastname: Ohta
authors.forename: Asao
authors.initials: A
authors.lastname: Katsume
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shimma
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sudoh
authors.forename: Takuo
authors.initials: T
authors.lastname: Tsukuda
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002951:Citrates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006207:Half-Life; D016174:Hepacivirus / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D010666:Phenylpropionates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D002951:Citrates; C507637:NA 255; D010666:Phenylpropionates