Enantioselective synthesis of derivatives and structure-activity relationship study in the development of NA255 as a novel host-targeting anti-HCV agent

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• 作者：Ken-ichi Kawasaki ; ^{kawasakikni@chugai-pharm.co.jp} ; Miyako Masubuchi ; Tadakatsu Hayase ; Susumu Komiyama ; Fumio Watanabe ; Hiroshi Fukuda ; Takeshi Murata ; Yasuaki Matsubara ; Kouhei Koyama ; Hidetoshi Shindoh ; Hiroshi Sakamoto ; Kohichi Okamato ; Atsunori Ohta ; Asao Katsume ; Masahiro Aoki ; Yuko Aoki ; Nobuo Shimma ; Masayuki Sudoh ; Takuo Tsukuda
• 关键词：HCV ; Host-targeting anti-HCV agent ; Serine palmytoyltransferase ; NA255 ; Natural product ; Total synthesis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：23
• 期：1
• 页码：336-339
• 全文大小：275 K

文摘

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.