Synthesis, structure and anticancer activity of novel 2,4-diamino-1,3,5-triazine derivatives

A series of 2-(4,6-diamino-1,3,5-triazin-2-yl)-2-{[4-(dimethylamino)-phenyl]imino}acetonitriles 19–27 have been synthesized by the reaction of 2-(4-amino-6-alkylamino-1,3,5-triazin-2-yl)acetonitriles 10–15 with p-nitrosodimethylaniline. Unexpectedly, a similar reaction of acetonitriles 10, 14, 15, 17 and 18 with nitrosobenzene led to the formation of 4,6-diamino-N-phenyl-1,3,5-triazine-2-carboxamides 28–32. The in vitro antitumor activity of the compounds obtained has been tested and 2-[4-Amino-6-(4-phenylpiperazin-1-yl)-1,3,5-triazin-2-yl]-2{[4-(dimethylamino)phenyl]imino}acetonitrile (19) having remarkable activity against melanoma MALME-3 M cell line (GI50 = 3.3 × 10–8 M, TGI = 1.1 × 10–6 M) is a leading candidate for further development.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide