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

Graphical abstract

Novel nucleosides were designed and synthesized by [3+2] cycloaddition, and showed moderate antiviral activities. The nucleosides were tested against 12 different viruses.

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.