Triazines and related products. Part 26. Synthesis and chemistry of bicyclic analogues of the antitumour drug 2,4,6-tris(dimethylamino)-1,3,5-triazine (hexamethylmelamine)

Abstract

Interaction of 2,4-bis(dimethylamino)-6-hydrazino-1,3,5-triazine (1c) with aryl aldehydes yields a series of aryl hydrazones (4) which cyclise to 3-aryl-5,7-bis(dimethylamino)-1,2,4-triazolo[4,3-a]-[1,3,5]triazines (6) with lead(IV) acetate in dichloromethane. Rearrangement of these bicycles in methanolic sodium hydroxide affords stable isomeric 2-aryl-5,7-bis(dimethylamino)[1,2,4]triazolo-[1,5-a][1,3,5]triazines (7). Selected examples from both series of triazolotriazines were screened against the mouse M5076 reticulum cell sarcoma and P388 leukaemia in vivo but proved to have no antitumour activity.