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Synthesis and in vitro anticancer activity of some novel cyclohepta[ b ]thiophene‐3‐carboxamides bearing pyrazole moiety
Author(s) -
AlGhorbani Mohammed,
Gouda Moustafa A.
Publication year - 2020
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4041
Subject(s) - chemistry , hydrazine (antidepressant) , cyanoacetamide , pyrazole , moiety , thiophene , malononitrile , hydrazide , phenacyl bromide , thiazole , hydrate , morpholine , acetylacetone , ethanol , pyridine , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis , chromatography
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 NaNO 2 /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.