Synthesis and properties of new substituted 1,2,4-triazoles: Potential antitumor agents

Cyclo addition of the reactive intermediates 4 with 1-(cyanomethyl)benzotriazole (5) and its N-2 isomer 9 furnished, after spontaneous rearrangements, the 1,2,4-triazole derivatives 8 and 10. Analogously, reaction of 4 with ethyl cyanoacetate lead to the 1,3,5-trisubstituted 1,2,4-triazoles 12, which gave on treatment with hydrazine the corresponding hydrazides 13. Treatment of 13d with galactose or phenyl isothiocayanate gave the 1-D-galactose-acylhydrazone 14 and the 1,2,4-triazole derivative 15, respectively. Compounds 8c; 10b,c; 13a,c and 14 were selected for the antitumor screening, whereby 8c, 13a, and 13c showed remarkable activity against leukemia, ovarian, renal and lung cancers (8c with Gl(50) of 0.70 muM, 0.07 muM against leukemia (CCRF-CEM and RPMI-8226), 0.02 muM against ovarian (OVCAR-3) and 0.60 muM against renal (CARKI-1) and lung cancers, respectively). (C) 2003 Elsevier Science Ltd. All rights reserved.