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

Abstract

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 1,2,4triazinone 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.

Synthesis of New Heterocyclic Nitrogen System Bearing Thiazolopyrazole Moiety as New Biocidal Agents

“…On the other hand, pyrazoles showed a very important medicinal and pharmacological properties [4]. Various heterocyclic nitrogen systems such as phathalazine [5] and 1,2,4-triazine derivatives reported as antimicrobial, anti HIV, anticancer and molluscicidal agents against snail [6][7][8][9][10]. Upon these observations, the present work tends to combination of these heterocyclic in one novel systems in view of their antibacterial in the compare with antibiotics.…”

Synthesis and antitumor activity of new isolated and fused heterobicyclic nitrogen systems containing 1,3,4-thiadiazole moiety derived from N1,N2-diaryl hydrazine compound

“…It is interesting to note that substituted pyrazoles exhibited a wide range of biological, pharmacological, and medicinal activities [15][16][17][18][19][20]. Recently, functionally 1,2,4-triazine derivatives showed an important biological activity such as anti-HIV, and anticancer [21], antioxidant [22], anti-inflammatory [23], antifungal [24], herbicidal [25] and antibacterial [26,27] agents. Also, 1,3,4thiadiazoles containingsmall heterocyclic nitrogen nucleus exhibited a greatspectrum biological activity as anti-inflammatory [28], anticancer [29,30], antimicrobial [31,32], anti-HIV, and antitumor [33], and antimycotic [34] agents.…”

Synthetic Approach for Novel Fluorine Substituted <i>α</i>-Aminophosphonic Acids Containing 1,2,4-Triazin-5-One Moiety as Antioxidant Agents

“…Phosphorus compounds bearing and/or containing 1,2,4-triazine moieties exhibit a significant attention due to the specific biological properties [13] [14] [15] [16] [17]. Also, the introduction of fluorine atoms to heterocyclic nitrogen systems, mostly improve their physical, chemical and medical properties [18] [19] [20] [21]. In the present work, we focused on the reactivity of functional 1,2,4-triazines towards different reagents followed by simple addition of diethyl phosphonate to obtain a novel fluorine substituted α-amino phosphonic acids which considered as α-amino acids analog, in view of antioxidant activity.…”