One-Pot Synthesis of 6-Amino-4-(furan/thiophen/pyrrol-2-yl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles, Evaluation of Anticancer Activity and Molecular Modelling Studies

Abstract

Pyrazoles with other heterocyclic scaffolds are important building blocks in many of the medicinally active new chemical entities. A facile one-pot multicomponent protocol for the synthesis of bioactive pyrano[2,3-c]pyrazoles was achieved by treating ethyl 3-oxobutanoate, hydrazine hydrate, five-membered heterocyclic aldehydes and malononitrile in the presence of in [BMIM]BF4 as medium at 70–75°C for 110–120 min with good yields of 85–90. This synthetic strategy has the remarkable advantages of excellent yields, straightforward protocol, being environment friendly, short reaction times and mild reaction condition. Here the need for catalyst and solvent are avoided by using the catalytically active ionic liquid as medium. In additional, the synthesized derivatives were assessed for cytotoxic potential against PANC-1 and SKOV-3 cells. Of the eight derivatives, one compound showed good cytotoxicity with an IC50 value of 8.5 and 9.1 µM against PANC-1 and SKOV-3 cells, respectively. Further, the docking studies revealed that this compound exhibited good binding energy (–7.3 kcal/mol) against human epidermal growth factor receptor protein.