Novel synthesis of pyran-3-hydrazide derivatives and their uses to the synthesis hydrazide-hydrazone, pyrazole and thiazole derivatives with anticancer activities

Abstract

ABSTRACT. The multi-component reaction of ethyl acetoacetate with each of malononitrile (3) benzaldehyde (1) in ethanol containing triethylamine gave the ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate (4). The latter compound reacted with hydrazine hydrate to give the hydrazide derivative 6. Compound 6 underwent a series of hetero-cyclization reactions to give pyrzole, hydraide-hydrazone, thiazole derivatives. The produced compounds tested against cancer cell lines six cancer cell lines and showed that compounds 8b, 10b, 11a, 17a, 21 and 24a were the most cytotoxic compounds. Further tests of the latter compounds toward the five tyrosine kinases and Pim-1 kinase showed that compounds 10b, 21 and 24a were the most potent of the tested compounds and compounds 10a, 11a and 17a were of the highest inhibitions toward Pim-1 kinase. The high inhibitions of most of the tested compounds toward the selected cancer cell lines and the tyrosine kinases encourage for future work to be done.

KEY WORDS: Hydrazide, Thiophene, Pyrazole, Pyran, Cytotoxicity, Tyrosine kinases

Bull. Chem. Soc. Ethiop. 2021, 35(3), 573-586. 

DOI: https://dx.doi.org/10.4314/bcse.v35i3.9