Synthesis and Antiviral Activity of certain Carbamoylpyrrolopyrimidine and Pyrazolopyrimidine Nucleosides

Article abstract of DOI:10.1021/jm00353a012

Following our recent discovery that 9-β-D-ribofuranosylpurine-6-carboxamide (1) exhibits potent antiviral activity, we were prompted to synthesize certain pyrrolopyrimidine and pyrazolopyrimidine nucleoside containing a carbamoyl function (7a,b and 13).The key precursor, 7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo<2,3-d>pyrimidine-4-carbonitrile (8a), required for the synthesis of 7a was prepared from the corresponding 4-chloro analogue (4a).Reaction of 4a with methanethiol, followed by oxidation, gave the 4-methylsulfonyl derivative (6a), which with NaCl in DMF gave 8a.Alkaline hydrolysis of 8a provided 7a.Similarly, 7b was prepared from 4-chloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo<3,4-d>pyrimidine (4b) via the carbonitrile intermediate 8b.Starting with thioformycin B or 7-chloro-3-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo<4,3-d>pyrimidine (10) and following the similar sequence of reactions, we obtained compound 13.The in vitro antiviral studies of these carbamoyl and certain related nucleosides indicated 7a to be a potent antiviral agent against vaccinia virus, whereas 13 was moderately active. 4-Chloro-7-β-D-ribofuranosylpyrrolo<2,3-d>pyrimidine was found to be one of the most active compounds against RVF, PICH, YF, and SF viruses in culture.