Synthesis and cytotoxic activity of some new heterocycles incorporating cyclohepta[b]thiophene‐3‐carboxamide derivatives

Abstract

A series of 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide-heterocyclic hybrids were synthesized, characterized and their cytotoxic potencies were assessed on four human cell lines. Cyanoacetamide derivative (5) was used as the key synthetic intermediate for the synthesis many derivatives in this study, derivatives 9, 11, 12 were formed by coupled compound 5 with different aryl/heteryl diazonium chlorides, Gewald reaction and Knoevenagel condensation were used for synthesis derivatives 13, 14, 16 by treated cyanoacetamide (5) with different reagents. In another route, compound 5 treated with phenyl isothiocyanate give thiocarbamoyl derivative (7) which used as intermediate underwent oxidative cyclization with different moieties to offer the corresponding thiazoles and thiophene 18, 19, 20, 21, respectively. in vitro cytotoxic activity of prepared compounds were tested against four human tumor cell lines. The result revealed that compound 11a displayed promising cytotoxic activity against HepG2, HCT-116, MCF-7, and PC3 cancer cell lines comparing to the positive control (Doxorubicin).

Recent contribution of medicinally active 2-aminothiophenes: A privileged scaffold for drug discovery

“…Typically, methodologies result in the formation of trisubstituted thiophene ring with an electron-withdrawing groups (EWG) -especially negative mesomeric effect such as carboxamide, ester or nitrile group on C3 position (Scheme 1). [8][9][10][11][12]…”

Green methodologies for the synthesis of 2-aminothiophene

“…Frequently, methodologies often lead to the formation of a trisubstituted thiophene ring with an electron-withdrawing group—particularly negative mesomeric effects like carboxamide, ester or cyano function on the C3 position (Fig. 2 ) (Minetto et al 2005 ; Revelant et al 2011 ; Gouda et al 2020 ; Hwang et al 2020 ; Ibrahim and Mohareb 2020 ).

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Catalyst-Free Site Selective Hydroxyalkylation of 5-Phenylthiophen-2-amine with α-Trifluoromethyl Ketones through Electrophilic Aromatic Substitution

“…Technically, it involves condensation of a carbonyl derivative, a α-cyanoester in the presence of sulfur source. To this day, used methodologies often undergo to the generation of trisubstituted thiophene ring with an electron withdrawing group–particularly negative mesomeric effect–on C 3 atom ( Figure 1 a) [ 11 , 12 , 13 , 14 , 15 ].…”