DIFFERENTIAL ANTIVIRAL ACTIVITY OF 2 TIBO DERIVATIVES AGAINST THE HUMAN IMMUNODEFICIENCY AND MURINE LEUKEMIA VIRUSES ALONE AND IN COMBINATION WITH OTHER ANTI-HIV AGENTS

R82913 and R86183, two derivatives of oimidazo[4,5,1-jk][1,4]-benzodia zepin-2(1H)-thione (TIBO), were found to potently and selectively inhi bit the replication and cell killing effects of a panel of biologicall y diverse laboratory and clinical strains of HIV-1. The two compounds exhibited significant activity in all human cell lines tested, as well as in fresh human peripheral blood lymphocytes and macrophages. One o f these two compounds (R82913) was found to significantly inhibit the replication of a murine retrovirus (Rauscher murine leukemia virus) in both UV-XC plaque formation and virus yield reduction assays. R86183, despite differing from R82913 only in the positioning of a single chl orine molecule, was not active against the murine retrovirus but was 1 0-fold more potent in inhibiting HIV-1 replication. Combination antivi ral assays with other reverse transcriptase inhibitors, including AZT, ddC, and carbovir, yielded synergistic anti-HIV activity with both TI BO derivatives. Additive to slightly synergistic results were obtained in combinations with ddI and phosphonoformic acid whereas additive to antagonistic activity was detected in combination with dextran sulfat e.