Synthesis and anti-hepatitis C virus (HCV) activity of 3′-C- substituted-methyl pyrimidine and purine nucleosides

Won Jun Choi; Yu Min Kim; Hea Ok Kim; Hyuk Woo Lee; Dong Eun Kim; Kwang Su Park; Youhoon Chong; Lak Shin Jeong

doi:10.1016/j.bmc.2010.05.002

Synthesis and anti-hepatitis C virus (HCV) activity of 3′-C- substituted-methyl pyrimidine and purine nucleosides

Won Jun Choi
, Yu Min Kim
, Hea Ok Kim
, Hyuk Woo Lee
, Dong Eun Kim
, Kwang Su Park
, Youhoon Chong
, Lak Shin Jeong

Department of Pharmacy

Ewha Womans University
Konkuk University

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

On the basis of potent anti-hepatitis C virus (HCV) activity of 2′-C-hydroxymethyladenosine, 3′-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from d-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y = OH, N₃, or F) at the 3′-C-substituted methyl position, among which 4g (Y = N₃) was the most potent, but it is also cytotoxic. This study guarantees the 3′-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents.

Original language	English
Pages (from-to)	4812-4820
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2010.05.002
State	Published - 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

3′-C-Azidomethyl nucleosides
3′-C-Fluoromethyl nucleosides
3′-C-Hydroxymethyl nucleosides
Anti-hepatitis C virus (HCV) activity
Neighboring group effect

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10.1016/j.bmc.2010.05.002

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@article{b8c013200b034ec28f06908074138de4,

title = "Synthesis and anti-hepatitis C virus (HCV) activity of 3′-C- substituted-methyl pyrimidine and purine nucleosides",

abstract = "On the basis of potent anti-hepatitis C virus (HCV) activity of 2′-C-hydroxymethyladenosine, 3′-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from d-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y = OH, N3, or F) at the 3′-C-substituted methyl position, among which 4g (Y = N3) was the most potent, but it is also cytotoxic. This study guarantees the 3′-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents.",

keywords = "3′-C-Azidomethyl nucleosides, 3′-C-Fluoromethyl nucleosides, 3′-C-Hydroxymethyl nucleosides, Anti-hepatitis C virus (HCV) activity, Neighboring group effect",

author = "Choi, \{Won Jun\} and Kim, \{Yu Min\} and Kim, \{Hea Ok\} and Lee, \{Hyuk Woo\} and Kim, \{Dong Eun\} and Park, \{Kwang Su\} and Youhoon Chong and Jeong, \{Lak Shin\}",

year = "2010",

doi = "10.1016/j.bmc.2010.05.002",

language = "English",

volume = "18",

pages = "4812--4820",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "13",

}

TY - JOUR

T1 - Synthesis and anti-hepatitis C virus (HCV) activity of 3′-C- substituted-methyl pyrimidine and purine nucleosides

AU - Choi, Won Jun

AU - Kim, Yu Min

AU - Kim, Hea Ok

AU - Lee, Hyuk Woo

AU - Kim, Dong Eun

AU - Park, Kwang Su

AU - Chong, Youhoon

AU - Jeong, Lak Shin

PY - 2010

Y1 - 2010

N2 - On the basis of potent anti-hepatitis C virus (HCV) activity of 2′-C-hydroxymethyladenosine, 3′-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from d-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y = OH, N3, or F) at the 3′-C-substituted methyl position, among which 4g (Y = N3) was the most potent, but it is also cytotoxic. This study guarantees the 3′-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents.

AB - On the basis of potent anti-hepatitis C virus (HCV) activity of 2′-C-hydroxymethyladenosine, 3′-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from d-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y = OH, N3, or F) at the 3′-C-substituted methyl position, among which 4g (Y = N3) was the most potent, but it is also cytotoxic. This study guarantees the 3′-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents.

KW - 3′-C-Azidomethyl nucleosides

KW - 3′-C-Fluoromethyl nucleosides

KW - 3′-C-Hydroxymethyl nucleosides

KW - Anti-hepatitis C virus (HCV) activity

KW - Neighboring group effect

UR - https://www.scopus.com/pages/publications/77954214576

U2 - 10.1016/j.bmc.2010.05.002

DO - 10.1016/j.bmc.2010.05.002

M3 - Article

C2 - 20627592

AN - SCOPUS:77954214576

SN - 0968-0896

VL - 18

SP - 4812

EP - 4820

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 13

ER -

Synthesis and anti-hepatitis C virus (HCV) activity of 3′-C- substituted-methyl pyrimidine and purine nucleosides

Abstract

UN SDGs

Keywords

Access to Document

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