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. 2009 Feb 15;19(4):1126-8.
doi: 10.1016/j.bmcl.2008.12.103. Epub 2008 Dec 31.

Synthesis of 5-isoxazol-5-yl-2'-deoxyuridines exhibiting antiviral activity against HSV and several RNA viruses

Yoon-Suk Lee  1 , Sun Min Park, Byeang Hyean Kim
Affiliations

Synthesis of 5-isoxazol-5-yl-2'-deoxyuridines exhibiting antiviral activity against HSV and several RNA viruses

Yoon-Suk Lee et al. Bioorg Med Chem Lett. .

Abstract

This paper describes a simple method for synthesizing a small library of 5-isoxazol-5-yl-2'-deoxyuridines from 5-iodo-2'-deoxyuridine. Nitrile oxides were generated in situ from oximes using a commercial bleaching agent; their cycloaddition with 5-ethynyl-2'-deoxyuridine yielded isoxazoles possessing activity against herpes simplex viruses 1 and 2, Encephalomyocarditis virus, Coxsackie B3, and vesicular stomatitis virus; these isoxazoles were, however, inactive against corona virus, influenza virus, and HIV.

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Figures

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Graphical abstract
Figure 1
Figure 1
C-5 isoxazole nucleosides.
Scheme 1
Scheme 1
Synthesis of 3–5. Reagents and conditions: (a) Ac2O, pyridine, rt, 8 h; yield 92%. (b) TMS-acetylene, Pd(PPh3)4, Et3N, DMF, 40 °C, 8 h; yield 87%. (c) KF, 10% MeOH in CH2Cl2; yield 80%.
Scheme 2
Scheme 2
Synthesis of oximes 6. Reagents and conditions: (a) HONH2·HCl, 1 N NaOH, THF (1:1), rt, 6 h; yield 90–99%.
Figure 2
Figure 2
Compounds tested for their antiviral properties against 12 different viruses.
Scheme 3
Scheme 3
Synthesis of 7 and 8. Reagents and conditions: (a) 4% NaOCl, THF, slow dropwise addition, rt, 10 h; yield 59–77%. (b) LiOH, MeOH/water (3:1), rt 10 h; yield 60–89%.
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References

    1. Bloom D.C., Devi-Rao G.B., Hill J.M., Stevens J.G., Wagner E.K. J. Virol. 1994;68:1283. - PMC - PubMed
    1. De Clercq E. J. Med. Chem. 2005;48:1297. - PubMed
    1. Bergstrom D.E., Ruth J.L., Reddy P.A., De Clercq E. J. Med. Chem. 1984;27:279. - PubMed
    2. De Clercq E., Descamps J., Verheht G., Walker R.T., Jones A.S., Torrence P.F., Shugar D. J. Infect. Dis. 1980;141:563. - PubMed
    3. Cheng Y.C., Grill S., Ruth J.L., Bergstrom D.E. Antimicrob. Agents Chemother. 1980;18:957. - PMC - PubMed
    1. Creuven I., Evrard C., Olivier A., Evrard G., Van Aerschot A., Wigerinck P., Herdewijn P., Durant F. Antiviral Res. 1996;30:63. - PubMed
    2. Wigerinck P., Pannecouque C., Snoeck R., Claes R., De Clercq E., Herdewijn P. J. Med. Chem. 1991;34:2383. - PubMed
    3. Wigerinck P., Kerremans L., Claes P., Snoeck R., Maudgal J.P., De Clercq E., Herdewijn P. J. Med. Chem. 1993;36:538. - PubMed
    1. Cecchi L., De Sarlo F., Machetti F. Eur. J. Org. Chem. 2006:4852.
    2. Himo F., Lovell T., Hilgraf R., Rostovtsev V.V., Noodleman L., Sharpless K.B., Fokin V.V. J. Am. Chem. 2005;127:210. - PubMed

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