Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 11: Structural modulations of diaryltriazines with potent anti-HIV activity

A series of novel 6-naphthyloxy substituted DATA analogues bearing different substituents on the C-6 position of triazine ring were synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cells. The results demonstrated that most of the compounds in this series are potent activity against HIV-1 with moderate to high selectivity. Among these analogues, two compounds exhibited excellent effect in inhibiting HIV-1 replication at nanomolar concentration (for compound 9h: IC50 = 9.3 nM, SI = 15,385; for compound 9i: IC50 = 9.4 nM, SI = 14,094), which are about 15-fold more active than nevirapine. In addition, several compounds are active against both HIV-1 and HIV-2, whose mechanism may be different from typical NNRTIs.

A number of diaryltriazine derivatives (DATAs) 8a–i and 9a–t were prepared and evaluated for their anti-HIV activity. Among which 9h and 9i were the most potent compounds with noteworthy selectivity against HIV-1 RT.Figure optionsDownload as PowerPoint slide