Design and Synthesis of Functionalized 2,4-Diamino-1,3,5-Triazines, Potential Inhibitors Involved in Immune and Inflammatory Response

A two-step synthesis method, initially using a microwave reactor for the preparation of reaction intermediates, allowed us to synthesize eleven 6-aryl-2,4-diamino-1,3,5-triazines 5a-k. The intermediates were biguanide derivatives 3a-f which were synthesized under microwave irradiation for 10 min at 130°C. The 2,4-diamino-1,3,5-triazine derivatives (5a-k) were obtained with yields from 16% to 86%. The compounds synthesized were submitted to biological evaluation on twelve protein kinases, through the implementation of a dose-response method which allowed the determination of median inhibitory concentration or IC₅₀. Indeed, enzymatic activities were carried out in the presence of 10 µM of ATP, in a final volume of 6 µl for 30 min at 30°C in ADP-Glo buffer. Among the triazines synthesized, results of enzymatic activity showed that the most active molecule was compound 5b which inhibited PIM1 kinase with IC₅₀ = 1.18 µg/mL This result is the starting point of a larger research program for our group which could investigate the introduction of the substituted group on triazine’s terminal amino group.