Fluorine Substituted 1,2,4-Triazinones as Potential Anti-HIV-1 and CDK2 Inhibitors

Abstract EN

Fluorine substituted 1,2,4-triazinones have been synthesized via alkylation, amination, and/or oxidation of 6-(2-amino-5-fluorophenyl)-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one 1 and 4-fluoro-N-(4-fluoro-2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)phenyl)benzamide 5 as possible anti-HIV-1 and CDK2 inhibitors.

Alkylation on positions 2 and 4 in 1,2,4-triazinone gave compounds 6–8.

Further modification was performed by selective alkylation and amination on position 3 to form compounds 9–15.

However oxidation of 5 yielded compounds 16–18.

Structures of the target compounds have been established by spectral analysis data.

Five compounds (5, 11, 14, 16, and 17) have shown very good anti-HIV activity in MT-4 cells.

Similarly, five compounds (1, 3, and 14–16) have exhibited very significant CDK2 inhibition activity.

Compounds 14 and 16 were found to have dual anti-HIV and anticancer activities.