Synthesis of Some Novel 2-{Pyrano[2,3-c]Pyrazoles-4-Ylidene}Malononitrile Fused with Pyrazole, Pyridine, Pyrimidine, Diazepine, Chromone, Pyrano[2,3-c]Pyrazole and Pyrano[2,3-d]Pyrimidine Systems as Anticancer Agents

Abstract

An unexpected efficient basic catalyzed heterocyclization reactions were carried out to build blocks of potentially bioactive 2-{pyrano[2,3-c]pyrazoles-4-ylidene}malononitrile skeleton fused with pyrazole, pyridine, pyrimidine, diazepine, chromone, pyrano[2,3-c]pyrazole, and pyrano[2,3-d]pyrimidine systems in novel molecular frames. The method depended on treatment of 6-amino-4-(4-oxo-4H-chromen-3-yl)-3-phenyl-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile (1) with different nitrogen and carbon nucleophiles in ethanolic sodium ethoxide. Possible mechanisms for the reactions were suggested. Elemental analyses and spectral techniques confirmed the structures of the isolated products. The compounds were evaluated for cytotoxic activities. Among the synthesized compounds, both 4 and 11 exhibited the most potent cytotoxicity against all used cancer cell lines.

Graphical Abstract

Keywords:

• Pyranopyrazole
• chromone
• nucleophiles
• nitrogen heterocycles
• cytotoxicity

Acknowledgments

The authors express their appreciation to "the Research Center for Advanced Materials Science (RCAMS)" at King Khalid University for funding this work under the grant number RCAMS/KKU/016-20.