Document Type : Original Article
Authors
1
Chemistry - Faculty of Science Zagazig Universty
2
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt
3
Department of Chemistry, Faculty of Science, Zagazig University, (Egypt)
4
Department of Chemistry, College of Science, Taif University, Taif, 21944, Saudi Arabia
Abstract
The present study reports the synthesis of some novel heterocyclic derivatives by reacting cyanoacetohydrazide in a basic medium with different electrophilic reagents. Initially, its reaction with H2O2 afforded 1,2,3-triazine-4,6(1H,5H)-dione, which upon addition to benzylidenemalononitrile under Michael's condition yielded 7-amino-4-oxo-5-phenyl-1,5-dihydro-4H-pyrano[2,3-d][1,2,3]triazine-6-carbonitrile. Azidolysis of cyanoacetohydrazide resulted in the formation of 5,8-dihydrotetrazolo[1,5-c][1,2,3]triazin-7-ol. On the other hand, heterocyclization of cyanoacetohydrazide with ethyl cyanoacetate and/or chloroacetyl chloride produced 2,5-dioxo-2,4,5,6-tetrahydro-1H-pyrazolo[1,5-b]pyrazole-3-carbonitrile and 3,5-dihydroxy-1,2-dihydropyridazine-4-carbonitrile, respectively. The later undergoes [2+3] intermolecular cycloaddition to the heteroallene system produced 4-(1,2,4-thiadiazol-3-yl)-1,2-dihydropyridazine-3,5-diol. Furthermore, Knoevenagel condensation and intramolecular heterocyclization of cyanoacetohydrazide with benzaldehyde and acetylacetone afforded 3-hydroxy-5-phenyl-4H-pyrazole-4-carbonitrile and 5,6a-dimethyl-3-oxo-1,2,3,6a-tetrahydro-3aH-furo[3,2-c]pyrazole-3a-carbonitrile, respectively. Intermolecular heterocyclization of cyanoacetohydrazide with diethyl oxalate and carbon disulphide gave 5-Hydroxy-2,3a-dihydropyrrolo[2,3-c]pyrazole-3,4-dione and 4-hydroxy-1,3a-dihydro-3H-pyrazolo[3,4-c]isothiazole-3-thione, respectively. All reactions proceeded in good to excellent yields and the synthesized compounds were identified by different spectroscopic techniques. All the obtained compounds are virtually screened by molecular docking on the target protein 1KZN by the MOE for potency as antibacterial agent. Also, pharmacophore and ADME studies were applied. Efficient binding to the target protein was found for some of the synthesized compounds.
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