Synthesis and antiviral activity of C-5 substituted analogues of d4T bearing methylamino- or methyldiamino-linker arms

A general strategy is reported for the preparation of C-5-methylamino- or m ethyldiamino-d4T analogues of "different sizes". Reactions of the 2',3'-did ehydro2',3'-dideoxy-C-5 hydroxymethyl precursor (7) with either polymethyle ne diamines (n = 6, 8, 10 and 12) or propargylamine proceed regioselectivel y via subtitution reactions at the C-5 position of uracil. The compounds we re evaluated for antiviral activity and cytotoxicity. No significant activi ty was observed for compounds 9, 11, and 13, but 10 and 12 exhibited a weak activity against HIV-1.