Benzene is a six-membered hydrocarbon ring system and if three carbon-hydrogen units of benzene ring are replaced by nitrogen atoms then triazine is formed. Triazines are present in three isomeric forms 1,2,3- triazine, 1,2,4-triazine, and 1,3,5-triazine according to the position of the nitrogen atom. These are weak bases having weaker resonance energy than benzene, so nucleophilic substitution is preferred than electrophilic substitution. Triazine is an interesting class of heterocyclic compounds in medicinal chemistry. Numerous synthetic derivatives of triazine have been prepared and evaluated for a wide spectrum of biological activities in different models with desired findings such as antibacterial, antifungal, anti-cancer, antiviral, antimalarial, antiinflammatory, antiulcer, anticonvulsant, antimicrobial, insecticidal and herbicidal agents. Triazine analogs have exposed potent pharmacological activity. So, triazine nucleus may be considered as an interesting core moiety for researchers for the development of future drugs.

Introduction: Cancer is still an untreatable disease and the second leading cause of death globally. The heterocyclic compounds have always played a major role in anticancer drug discovery program. 1,2,4-Triazine-6-ones is a heterocyclic privileged structure with diversified activities. In the presented study 21 Novel 2,5-disubstituted-3-phenyl-1,2-dihydro-1,2,4-triazin-6 (5H)-one derivatives (13(a-k), 18(a-j) and 21(a1-a4, b)) have been synthesized and tested for their anticancer activity. Methods: The 2,5-disubstituted-3-phenyl-1,2-dihydro-1,2,4-triazin-6(5H)-one derivatives (13(a-k), 18(a-j) and 21(a1-a4, b) were synthesized by refluxing substituted-2-phenyloxazol-5(4H)-one and hydrazine derivatives. Substituted aldehydes were synthesized via Vilsmeier-Haack reaction, while substituted-2-phenyloxazol-5(4H)-one derivatives were synthesized by Erlenmeyer Plochl azalactone synthesis. Twenty-one compounds were selected and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10-5M) in full NCI 60 cell panel assay. Results and Conclusion: The selected compounds (13a, 13b, 13c, 13f, 13h, 13i, 13j, 18h, 18i, 21a4) were found to be an active against different cancer cell lines. The compound, 5-((5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)-2-(4-nitrobenzoyl)-3-phenyl-1,2-dihydro-1,2,4-triazin-6(5H)-one (13a) was found to be potent anti-cancer agent as electron rich moiety on phenyl at position 2 of triazine nucleus has great impact on anticancer activity.