Synthesis and antiviral activity of several 2,5'-anhydro analogs of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AZU), 3'-azido-2',3'-dideoxy-5-halouridines, and 3'-deoxythymidine against human immunodeficiency virus (HIV-1) and Rauscher-Murine leukemia virus (R-MuLV)
Several 2,5''-anhydro analogoues of 3''-azido-3''-deoxythymidine (AZT), 3''-azido-2'',3''-dideoxyuridine (AZU), 3''-azido-2'',3''-dideoxy-5-bromouridine, 3''-azido-2'',3''-dideoxy-5-iodouridine, and 3''-deoxythymidine and the 3''-azido derivative of 5-methyl-2''-deoxyisocytidine have been synthesized for evaluation as potential anti-HIV (human immunodeficiency virus) agents. These 2,5''-anhydro derivatives, compounds 13-17, demonstrated significant anti-HIV-1 activity with IC50 values of 0.56, 4.95, 26.5, 27.1, and 48 .mu.M, respectively. Compared to that of the parent compounds AZT and AZU, the respective 2,5''-anhydro analogoues, compounds 13 and 14, were somewhat less active. Whereas AZT was cytotoxic with a TCID50 of 29 .mu.M, the toxicity of the 2,5''-anhydro derivative of AZT, compound 13, was reduced considerably to a TCID50 value of > 100 .mu.M. The 2,5''-anhydro analogue of 5-methyl-2''-deoxyisocytidine also demonstrated anti-HIV-1 activity with an IC50 value of 12 .mu.M. These compounds were also evaluated against Rauscher-Murine leukemia virus (R-MuLV) in cell culture. Among them, AZT, 3''-azido-2'',3-dideoxy-5-iodouridine, 3''-azido-2'',3''-dideoxy-5-bromouridine, and 2,5''-anhydro-3''-azido-3''-deoxythymidine (13) were found to be most active, with IC50 values of 0.023, 0.21, 0.23, and 0.27 .mu.M, respectively.