Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide
The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide. The latter was used to synthesize different heterocyclic derivatives comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2010-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/16/1/52/ |
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| author | Amira E. Mahmoud Maher H. Helal Rafat M. Mohareb Hoda Z. Shams |
| author_facet | Amira E. Mahmoud Maher H. Helal Rafat M. Mohareb Hoda Z. Shams |
| author_sort | Amira E. Mahmoud |
| collection | DOAJ |
| description | The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide. The latter was used to synthesize different heterocyclic derivatives comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine, and coumarin rings. The mechanistic and synthetic pathways depended on regioselective attack and/or cyclization by the cyanoacetamido moiety in the key precursor on various chemical reagents. The competition of the reaction pathways including dipolar cyclization, dinucleophilic-bielectrophilic attack, β-attack, Gewald-type attack, and condensation reactions led to the diversity of the synthesized products. The antitumor activities of the synthesized products were studied and evaluated. Most of the compounds revealed high inhibitory effects when screened in vitro for their antiproliferative activity. Three human cancer cell lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were used in the screening tests. The simplicity of the synthetic procedures which mainly involved one-pot reactions under mild reaction conditions, the convenience of yield production and the diversity of the reactive sites in the produced systems play a valuable role for further heterocyclic transformations and further biological investigations. |
| first_indexed | 2024-04-13T06:27:22Z |
| format | Article |
| id | doaj.art-4fcd435474f1479f8470cddb4daf5551 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T06:27:22Z |
| publishDate | 2010-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4fcd435474f1479f8470cddb4daf55512022-12-22T02:58:22ZengMDPI AGMolecules1420-30492010-12-01161527310.3390/molecules16010052Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamideAmira E. MahmoudMaher H. HelalRafat M. MoharebHoda Z. ShamsThe reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide. The latter was used to synthesize different heterocyclic derivatives comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine, and coumarin rings. The mechanistic and synthetic pathways depended on regioselective attack and/or cyclization by the cyanoacetamido moiety in the key precursor on various chemical reagents. The competition of the reaction pathways including dipolar cyclization, dinucleophilic-bielectrophilic attack, β-attack, Gewald-type attack, and condensation reactions led to the diversity of the synthesized products. The antitumor activities of the synthesized products were studied and evaluated. Most of the compounds revealed high inhibitory effects when screened in vitro for their antiproliferative activity. Three human cancer cell lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were used in the screening tests. The simplicity of the synthetic procedures which mainly involved one-pot reactions under mild reaction conditions, the convenience of yield production and the diversity of the reactive sites in the produced systems play a valuable role for further heterocyclic transformations and further biological investigations.http://www.mdpi.com/1420-3049/16/1/52/4,5,6,7-tetrahydrobenzo[b]thiophenethiazolepyrazolepyridineantitumor |
| spellingShingle | Amira E. Mahmoud Maher H. Helal Rafat M. Mohareb Hoda Z. Shams Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide Molecules 4,5,6,7-tetrahydrobenzo[b]thiophene thiazole pyrazole pyridine antitumor |
| title | Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide |
| title_full | Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide |
| title_fullStr | Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide |
| title_full_unstemmed | Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide |
| title_short | Novel Synthesis and Antitumor Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide |
| title_sort | novel synthesis and antitumor evaluation of polyfunctionally substituted heterocyclic compounds derived from 2 cyano n 3 cyano 4 5 6 7 tetrahydrobenzo b thiophen 2 yl acetamide |
| topic | 4,5,6,7-tetrahydrobenzo[b]thiophene thiazole pyrazole pyridine antitumor |
| url | http://www.mdpi.com/1420-3049/16/1/52/ |
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