Synthesis and biological evaluation of piperidine-substituted triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors

A novel series of piperidine-substituted triazine derivatives have been synthesized and evaluated for anti-HIV activities in MT-4 cells. Most compounds displayed extremely promising activity against wild-type HIV-1 with EC50 values in low nanomolar concentration, better than that of Nevirapine, Delavirdine, Zidovudine and Dideoxycitidine, and higher potency towards the resistant mutant strain K103N/Y181C than that of Nevirapine and Delavirdine. Selected compounds were also assayed against reverse transcriptase with lower IC50 values than that of Nevirapine. The structure-activity relationship (SAR) of these novel structural congeners was also discussed.

Graphical abstractThe novel piperidine-substituted triazine derivatives showed extremely promising activity against wild-type HIV-1 and moderate potency towards the K103N/Y181C resistant mutant strain.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel piperidine-substituted triazine derivatives were synthesized. ► Promising activity against wild-type HIV-1 (EC50 = 7.0 nM, SI = 3240). ► IC50 values against HIV-1 RT were in low micromolar level.