Synthesis of Novel Heterocyclic Compounds Incorporate 4,5,6,7-Tetrahydrobenzo[<i>b</i>]thiophene Together with Their Cytotoxic Evaluations

Abstract

The 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene was the key starting compound used to synthesize new thiazole, pyrimidine, pyran, pyridine and thiazine derivatives. The cytotoxicity of the synthesized compounds was studied towards the three cancer cell lines namely MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (central nervous system (CNS) cancer) in addition to the normal cell line (WI-38) using doxorubicin as the reference drug. The study showed that compounds 5, 9a, 15b, 17c, 18 and 21b were the most potent compounds. anti-leishmanial agents, 11) antioxidant activity, 12) anti-arrhythmic, serotonin antagonist and anti-anxiety activities. Key words 13)Recently we were involved through the synthesis of polyfunctional heterocyclic compounds, where the 2-cyanomethylbenzo[c] imidazole was used as the key starting compound.14) In addition, we were involved through the reaction of ethyl acetoacetate with elemental sulphur and either malononitrile or ethyl cyanoacetate gave thiophene derivatives. 15) In the present work we were concerned through exploring the reactivity of the amino group present in the 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b] thiophene 16) towards different chemical reagents to afford a vast number of heterocyclic compounds involving tetrahydrobenzo[b]-thiophene moiety and evaluating their cytotoxicity. Results and DiscussionChemistry The reaction of the 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b] thiophene with triethyl orthoformate in acetic acid gave the ethyl N- (3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) formimidate 1. The analytical and spectral data of compound 1 were the tools of its structural elucidation. Compound 1 reacted with aniline to give the N-phenyl formamidine derivative 2. The elemental and spectral data of compound 2 were consistent with its proposed structure. Thus, 1 H-NMR spectrum of compound 2 showed, beside the expected signals, a singlet at 6.95 ppm δ for CH moiety, a muliplet at δ 7.27-7.90 ppm for phenyl ring and a singlet at δ 8.36 ppm for NH group. On the other hand, the reaction of compound 1 with malononitrile gave the imino-methyl malononitrile derivative 3. The analytical and spectral data of compound 3 were in agreement with its structure (see Experimental section). The reaction of compound 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b] thiophene with phenylisothiocyanate and chloroacetone gave the thiazole derivative 5. Formation of the latter product took place through the intermediate formation of 4 followed by water elimination (Chart 1).Next we studied the possibility of compound 2-amino-3-cyano-4, 5,6,7-tetrahydrobenzo[b] thiophene to form thiourea derivative. Thus, compound 2-amino-3-cyano-4, 5,6,7-tetrahydrobenzo[b] thiophene reacted with phenyl

Synthesis and Anticancer Evaluations of Novel Thiazole Derivatives Derived from 4-Phenylthiazol-2-amine

“…In continuation of our previous work, [31][32][33][34][35][36][37][38] the current study reported synthesizing some novel thiazole de- rivatives based on 4-phenylthiazol-2-amine. The anticancer activity for all the synthesized compounds was evaluated.…”

Synthesis of Heterocyclic Compounds Derived From Dimedone and their Anti-tumor and Tyrosine Kinase Inhibitions

“…The reaction of dimedone (1) with any of the aromatic aldehydes 2a-c gave the benzylidene derivatives 3a-c, respectively. Compounds 3a-c were appropriate for Gewald's thiophene synthesis [24][25][26] through the reaction of any of compounds 3a-c with either of malononitrile (4a) or ethyl cyanoacetate (4b) and elemental sulfur gave the 6,7-dihydrobenzo[b]thiophen-5(4H)-one derivatives 5a-f, respectively. The structures of compounds 5a-f were based on their analytical and spectral data.…”

Novel synthesis of pyran, thiophene, and pyridine derivatives incorporating thiazole ring and their antitumor evaluation

“…In the current work, we are explaining the synthesis of thiazole derivatives together with their antitumor evaluation, in proceedings to our concern in synthesize of bioactive heterocyclic compounds. Thus, compound ( 1 ) 2‐(4‐oxo‐4,5‐dihydrothiazol‐2‐yl)acetonitrile, which was obtained as reported in literature by the reaction of malononitrile with thioglycolloic acid in acetic acid solution, reacted with any of acetphenone, 4‐chloroacetophenone, or 4‐methylacetophenone in an oil bath at 120°C to afford the respective compounds 2a‐c through the Knoevenagel reaction (Scheme ).…”