Synthesis, antiretrovirus effects and phosphorylation kinetics of 3'-isocyano-3'-deoxythymidine and 3'-isocyano-2',3'-dideoxyuridine

1 February 1990

journal article
research article
Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry

Vol. 33 (2) , 845-848
https://doi.org/10.1021/jm00164a059

Abstract

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 .fwdarw. RN .dbd.P (C6H5) .fwdarw. 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 (Ki) for MT-4 cell dThd kinase than ddUrd derivative 12. Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase.

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