Structure-based bioisosterism design, synthesis and biological evaluation of novel 1,2,4-triazin-6-ylthioacetamides as potent HIV-1 NNRTIs

The 1,2,4-triazin-6-ylthioacetamides were identified as potent NNRTIs designed by structure-based bioisosterism strategy. The HIV-1(IIIB) inhibitory activity of compound 8b15 (EC50 = 0.018 ± 0.007 μM) was about seventy-eight, eleven and two fold more active than that of positive control drugs DDC, NVP and DLV respectively, and displayed similar anti-HIV-1 activity as that of EFV. Because of their excellent potency, these 1,2,4-triazin-6-yl thioacetamide derivatives may have antiviral potential and should be further pursued as next-generation NNRTIs.