Comparative activity of 2′,3′-saturated and unsaturated pyrimidine and purine nucleosides against human immunodeficiency virus type 1 in peripheral blood mononuclear cells

Recently, the anti-HIV-1 activities of 2',3'-dideoxy-2',3'-didehydronucleosides such as D4C, D4T, 2',3'-dideoxy-2',3'-didehydroadenosine (D4A) and the corresponding guanine analogue, d4G, were reported. As a part of continuing efforts to study nucleosides as anti-HIV-1 agents, the structure-activity relationships of various 2',3'-dideoxy-2',3'-didehydro-pyrimidine and purine nucleosides, including some C-nucleosides, are reported. A human peripheral blood mononuclear (PBM) cell screening system was used to determine the antiviral activity. Since 3'-azido-5-ethyl-2',3'-dideoxyuridine (CS-85) and CS-87 are compounds that have been reported to have antiviral activity and low bone marrow toxicity in culture, it was of interest to synthesize the 3'-unsubstituted 2',3'-saturated and 2',3'-unsaturated analogues of CS-85 and CS-87.