Synthesis and in vitro anticancer activity of some novel cyclohepta[b]thiophene-3-carboxamides bearing pyrazole moiety

摘要

2-Aminothiophene 3 was achieved through the one-pot multicomponent reaction of cycloheptanone, cyanoacetamide, elemental sulfur, and morpholine in ethanol. Diazotization of 2-aminothiophene 3 with NaNO2/HCl gave the corresponding diazonium salt 4, that combined with the appropriate active methylene components; 5a, 5b, 7, 11, 13, 16, 18, 21, 9, 19, 22a, and 22b in pyridine (AcONa/EtOH) to form the corresponding hydrazones 6a, 6b, 8, 10, 14, 15, 17, 20, 23, 24, 25a, and 25b, respectively. Heating of compound 8 with malononitrile 9 in ethanol gave the thiazole 10. Treatment of compound 10, 25a, and 25b with hydrazine hydrate achieve the pyrazoles 12, 27a, and 27b, respectively. Hydrazinolysis of compound 14 with hydrazine hydrate, followed by condensation of the obtained hydrazide 15 with acetylacetone 19 gave the pyrazole 20. The recently orchestrated thiophenes were assessed for their cytotoxic action. The result revealed that compound 12 indicated comparable and better action towards HePG2, HCT-116, MCF-7, and PC3 cancer cell lines than Doxorubicin.