Synthesis and Antiviral Activity of Some 7-pyrazolopyrimidine Analogues of Sangivamycin and Toyocamycin

Article abstract of DOI:10.1021/jm00169a027

The sodium salt of 4-amino-3-cyanopyrazolo<3,4-d>pyrimidine (1) was condensed with (2-acetoxyethoxy)methyl bromide (2) to provide the corresponding protected acyclic nucleoside, 4-amino-3-cyano-1-<(2-acetoxyethoxy)methyl>pyrrazolo<3,4-d>pyrimidine (3).Treatment of 3 with sodium methoxide in methanol provided a good yield of methyl 4-amino-1-<(2-hydroxyethoxy)methyl>pyrrazolo<3,4-d>pyrimidine-3-formimidate (4).Treatment of the imidate (4) with sodium hydrogen sulfide gave the thiocarboxamide derivative 5.Aqueous base transformed 4 into 4-amino-1<(2-hydroxyethoxy)methyl>pyrrazolo<3,4-d>pyrimidine-3-carboxamide (6) in good yield.Treatment of 5 with mercuric chloride furnished the toyocamycin analogue 7.Evaluation of compounds 1, 3-7 revealed that only the heterocycle (1) and the thiocarboxamide acyclic nucleoside (5) were active.Compound 5 was the more potent with activity against human cytomegalovirus and herpes simplex virus type 1.