Synthesis, Antiretrovirus Effects, and Phosphorylation Kinetics of 3'-Isocyano-3'-deoxythymidine and 3'-Isocyano-2',3'-dideoxyuridine

Article abstract of DOI:10.1021/jm00164a059

The silylated AzddThd 5 and AzddUrd 6 prepared from 2,3'-anhydronucleoside derivatives 3 and 4 were transformed to formamides 7 and 8 by using the sequence RN3 -> RN=P(C6H5) -> RNHCHO.Formamides 7 and 8 were dehydrated to the protected 3'-isocyano derivatives 9 and 10; deblocking gave 11 and 12.Neither 3'-isocyano-3'-deoxythymidine (11) nor 3'-isocyano-2',3'-dideoxyuridine (12) showed anti-HIV activity at noncytotoxic concentrations. ddThd derivative 11 was considerably more toxic to MT-4 cells than ddUrd derivative 12; it also had a much greater affinity (K_i) forMT-4 cell dThd kinase than ddUrd derivative 12.Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase.