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Several 2,3-diaryl-1,3-thiazolidin-4-ones were synthesized and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of HIV-1 replication at 30–50 nM concentrations with minimal cytotoxicity, thereby acting as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).