Synthesis and biological evaluation of nucleoside analogues having 6-chloropurine as anti-SARS-CoV agents

Masahiro Ikejiri; Masayuki Saijo; Shigeru Morikawa; Shuetsu Fukushi; Tetsuya Mizutani; Ichiro Kurane; Tokumi Maruyama

doi:10.1016/j.bmcl.2007.02.026

Synthesis and biological evaluation of nucleoside analogues having 6-chloropurine as anti-SARS-CoV agents

Bioorg Med Chem Lett. 2007 May 1;17(9):2470-3. doi: 10.1016/j.bmcl.2007.02.026. Epub 2007 Feb 13.

Authors

Masahiro Ikejiri¹, Masayuki Saijo, Shigeru Morikawa, Shuetsu Fukushi, Tetsuya Mizutani, Ichiro Kurane, Tokumi Maruyama

Affiliation

¹ Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.

Abstract

Nucleoside analogues that have 6-chloropurine as the nucleobase were synthesized and evaluated for anti-SARS-CoV activity by plaque reduction and yield reduction assays in order to develop novel anti-SARS-CoV agents. Among these analogues, two compounds, namely, 1 and 11, exhibited promising anti-SARS-CoV activity that was comparable to those of mizoribine and ribavirin, which are known anti-SARS-CoV agents. Moreover, we observed several SAR trends such as the antiviral effects of the 6-chloropurine moiety, unprotected 5'-hydroxyl group and benzoylated 5'-hydroxyl group.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology*
Chemistry, Pharmaceutical / methods
Chlorocebus aethiops
Dose-Response Relationship, Drug
Drug Design
Evaluation Studies as Topic
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Nucleosides / chemical synthesis*
Nucleosides / pharmacology*
Purines / chemistry*
Severe Acute Respiratory Syndrome / drug therapy*
Severe acute respiratory syndrome-related coronavirus / metabolism*
Vero Cells

Substances

Antiviral Agents
Nucleosides
Purines
6-chloropurine