Synthesis of Novel 4-Alkylidene- and 4-Alkylamino-5-oxo-4,5-Dihydro-[1,2,4] triazole Derivatives and Investigation of Their Antitumor Activities


Abstract: A series of novel 3-alkyl-4-cyclohexylmethylenamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (6a-e) and 3-alkyl-4-hexylidenamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (7b-e) were synthesized from the reaction of corresponding 3-alkyl-4-amino-5-oxo-4,5-dihydro-[1,2,4]triazoles (1) with cyclohexancarboxaldehyde and capronaldehyde. The acetylation of compounds 6e and 7b resulted in the formation of 1-acetyl-4- cyclohexylmethylenamino-5-oxo-3-(p-tolyl)-4,5-dihydro-[1,2,4]triazole (10) and 3-benzyl-4-hexylidenamino-5-oxo-4,5-dihydro-[1,2,4]triazole (11). 3-Alkyl-4-cyclohexylmethylamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (8a-e) and 3-alkyl-4-hexylamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (9b-e) were obtained from the selective reduction of compounds 6a-e and 7b-e with NaBH_4. The in vitro antitumor activity of some selected compounds was screened by the National Cancer Institute (USA) against several human tumor cell lines, and compounds 8c, 9d and 11c were found to be active.

Keywords: Imine bond, antitumor activity, capron aldehyde, cyclohexane carboxaldehyde, 5-oxo-[1,2,4]triazole

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