Synthesis and antiviral activity of various 3'-azido analogs of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1, HTLV-III/LAV)

Abstract
Various 3''-azido analogues of pyrimidine deoxyribonucleosides have been synthesized and tested against human immunodeficiency virus (HIV-1, HTLV-III/LAV) in human peripheral blood mononuclear cells. Among these compounds, the 3''-azido analogues of thymidine (2), 3-(3-oxo-1-propenyl)thymidine (21), 2''-deoxyuridine (1), 2''-deoxy-5-bromouridine (5), 2''-deoxy-5-fluorocytidine (19), 2''-deoxy-5-iodouridine (6), 2''-deoxycytidine (18), 2''-deoxy-5-fluorouridine (4), 2''-deoxy-5-thiocyanatouridine (16), 2''-deoxy-5-methylcytidine (20), 2''-deoxy-5-aminouridine (7), and 2''-deoxy-5-hydroxyuridine (10) were found to have significant antiviral activity, with EC50 values of 0.002, 0.01, 0.2, 1.0, 1.0, 1.1, 1.2, 4.8, 5.1, 5.1, 6.2, and 10 .mu.M, respectively. The structure-activity relationships are discussed.

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