Synthesis and evaluation of the anti-hepatitis B virus activity of 4 '-Azido-thymidine analogs and 4 '-Azido-2 '-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent

摘要

Hepatitis B virus (HBV) infection is a major worldwide health problem that requires the development of improved antiviral therapies. Here, a series of 4 '-Azido-thymidine/4 '-Azido-2 '-deoxy-5-methylcytidine derivatives (6, 10-15) were synthesized, and their anti-HBV activities evaluated. Compounds 10-15 were synthesized via an SNAr reaction of 18, in which the 4-position of the thymine moiety was activated as the 2,4,6-triisopropylbenzenesulfonate. Compounds 11-15 showed no antiviral activity. However, 4 '-Azido thymidine (6) and 4 '-Azido-2 '-deoxy-5-methylcytidine (10) displayed significant anti-HBV activity (EC50 = 0.63 and 5.99 mu M, respectively) with no detectable cytotoxicity against MT-2 cells up to 100 mu M.