A pyrimidine–pyrazolone nucleoside chimera with potent in vitro anti-orthopoxvirus activity

5-Formyl-2′-deoxyuridine was condensed with 1-phenyl-3-methyl-2-pyrazolin-5-one to give a novel pyrimidinylidene–pyrazolone nucleoside ( 9) with potent in vitro anti-orthopoxvirus properties. Synthetic hybridization of two privileged drug scaffolds, pyrazolone on the one hand and pyrimidine nucleoside on the other, resulted in the generation of two novel 5-substituted pyrimidine nucleosides with potent in vitro antiviral activity against two representative orthopoxviruses, vaccinia virus and cowpox virus.