Synthesis and Evaluation of Novel Pyrido[1,2-b][1,2,4]triazine-2,6-dione and Pyrido[1,2-b][1,2,4]triazepine-2,7-dione Derivatives as Antioxidant Agents

Background: During the last years, condensed pyridine compounds have received much attention because of their immense biological properties. In this article, a practical and efficient synthesis of their novel series pyrido[1,2-b][1,2,4]triazine-2,6-dione and pyrido[1,2-b][1,2,4]triazepine-2,7-dione derivatives has been developed. Method: Different epoxides and substituted 1,6-diaminopyridone have been used. The reaction occurred preferentially with the regioselective opening of the epoxides by the N-amino group (N-NH2) of 1,6-diaminopyridone to form the instable intermediates cyanohydrins, which loses hydrogen cyanide giving intermediate acylcyanide or α-keto esters which underwent a cycloaddition reaction between the other amino group at (C-NH2) and the second elecrophilic carbon of the epoxide affording the target pyrido[1,2-b][1,2,4]triazine-2,6-diones and pyrido[1,2-b][1,2,4]triazepine-2,7-diones respectively. The structural assignments of these compounds were made on the basis of spectroscopic data (IR, 1H NMR, 13C NMR and Mass) and elemental analysis. The synthesized compounds were evaluated for their antioxidant (DPPH, FRAP and ABTS assays). Result: The synthesized compounds with different substituent’s were obtained in good yields. Most of the compounds were found to be more active in DPPH, FRAP and ABTS assays. Conclusion: We have successfully synthesized two series of novel fused nitrogen heterocyclic systems such as pyrido[1,2-b][1,2,4]triazine-2,6-diones and pyrido[1,2b][1,2,4] triazepine-2,7-diones. This process offers several advantages: shorter time, operational simplicity, mild reaction conditions and ease of products isolation. A series of compounds showed significant antioxidant activity and seem to be of interest for industrial and medical uses and results from this study suggest their incorporation in toxicological and pharmacological studies.