POTENT AND SPECIFIC-INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1REPLICATION BY 4-(2,6-DICHLOROPHENYL)-1,2,5-THIADIAZOL-3-YL N,N-DIALKYLCARBAMATE DERIVATIVES

4-(2,6-Dichlorophenyl)-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA ) derivatives were found to be highly potent and;specific inhibitors o f human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell cultures. The most potent congener of TDA derivatives, RD4-20 24, inhibited HIV-1 replication by 50% at concentrations of 12.5 and 4 .8 nM in MT-4 cells and peripheral blood mononuclear cells, respective ly. These concentrations were more than 2,000- and 30,000-fold lower t han its 50% cytotoxic concentrations, respectively. Although the TDA d erivatives were active against 3'-azido-3'-deoxythymidine-resistant HI V-1, no antiviral activities were observed against HIV-2 and nonnucleo side reverse transcriptase inhibitor-resistant mutants of HIV-1. The T DA derivatives inhibited recombinant HIV-1 reverse transcriptase activ ity, depending on the template-primer used for the assay. However, the y did not interact with HIV-2 reverse transcriptase. Thus, the TDA der ivatives belong to the family of nonnucleoside reverse transcriptase i nhibitors. Because of their potent anti-HIV-1 activities in vitro and their low levels of toxicity in mice, the TDA derivatives deserve furt her evaluation as candidate drugs for the treatment of patients with A IDS.