5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents

Masahiro Ikejiri, Takayuki Ohshima, Keizo Kato, Masaaki Toyama, Takayuki Murata, Kunitada Shimotohno, Tokumi Maruyama

研究成果: Article

11 引用 (Scopus)

抄録

On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5′-O-masked analogues of 6-chloropurine-2′-deoxyriboside (e.g., 5′-O-benzoyl, 5′-O-p-methoxybenzoyl, and 5′-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5′-O-benzoyl analogue exhibited the highest potency with an EC50 of 6.1 μM in a cell-based HCV replicon assay. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC50 = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5′-O-masked analogues: One is the role as an anti-HCV agent by itself, and the other is as a prodrug of its 5′-O-demasked (deprotected) derivative.

元の言語English
ページ(範囲)6882-6892
ページ数11
ジャーナルBioorganic and Medicinal Chemistry
15
発行部数22
DOI
出版物ステータスPublished - 15-11-2007
外部発表Yes

Fingerprint

Lead compounds
Viruses
Hepacivirus
Hydroxyl Radical
Therapeutics
Severe Acute Respiratory Syndrome
Replicon
Coronavirus
Prodrugs
Nucleosides
Ether
Antiviral Agents
Assays
2'-deoxyadenosine
Derivatives

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

Ikejiri, Masahiro ; Ohshima, Takayuki ; Kato, Keizo ; Toyama, Masaaki ; Murata, Takayuki ; Shimotohno, Kunitada ; Maruyama, Tokumi. / 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents. :: Bioorganic and Medicinal Chemistry. 2007 ; 巻 15, 番号 22. pp. 6882-6892.
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5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents. / Ikejiri, Masahiro; Ohshima, Takayuki; Kato, Keizo; Toyama, Masaaki; Murata, Takayuki; Shimotohno, Kunitada; Maruyama, Tokumi.

:: Bioorganic and Medicinal Chemistry, 巻 15, 番号 22, 15.11.2007, p. 6882-6892.

研究成果: Article

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AU - Ikejiri, Masahiro

AU - Ohshima, Takayuki

AU - Kato, Keizo

AU - Toyama, Masaaki

AU - Murata, Takayuki

AU - Shimotohno, Kunitada

AU - Maruyama, Tokumi

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