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 (GI(50)=3.3 x 10(-8) M, TGI=1.1 x 10(-6) M) is a leading candidate for further development.
Saczewski
F
F
Department of Chemical Technology of Drugs, Medical University of Gdańsk, 80-416 Gdańsk, Poland. saczew@amg.gda.pl
Bułakowska
A
A
Bednarski
P
P
Grunert
R
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014227:Triazines