Discovery of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors
Abstract
1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Biological Evaluation
2.3. Docking Study
3. Experimental Section
3.1. Chemistry
3.1.1. Synthesis of 4-(Thiophen-2-ylthio)butanoic Acid (1)
3.1.2. Synthesis of 6,7-Dihydrothieno[2,3-b]thiepin-4(5H)-one (2)
3.1.3. Synthesis of Methyl Oxo(4-oxo-4,5,6,7-tetrahydrothieno[2,3-b]thiepin-5-yl)acetate (3)
3.1.4. Synthesis of Methyl 4,5-dihydro-1H-thieno[2′,3′:2,3]thiepino[4,5-c] pyrazole-3-carboxylate (4)
3.1.5. Synthesis of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepin[4,5-c]pyrazole-3-carboxylic acid (5)
3.1.6. General Procedure for the Synthesis of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino[4,5-c]pyrazole-3-carboxamides (6a–6l)
3.2. Cell Proliferation Assay
3.3. Molecular Docking
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the all target compounds are available from the authors. |
No. | Substituents | IC50 (μM) | |
---|---|---|---|
A549 | HepG2 | ||
6a | 4-methylpiperazin-1-yl | 23.44 ± 3.32 | >200 |
6b | 4-phenylpiperazin-1-yl | 21.38 ± 14.39 | >200 |
6c | 4-(4-methylphenyl)piperazin-1-yl | 11.03 ± 1.96 | >200 |
6d | 4-(4-methoxyphenyl)piperazin-1-yl | 13.13 ± 1.21 | >200 |
6e | 4-(4-fluorophenyl)piperazin-1-yl | 92.71 ± 23.90 | >200 |
6f | 4-(2-methylphenyl)piperazin-1-yl | 3.79 ± 13.39 | >200 |
6g | 4-(2-fluorophenyl)piperazin-1-yl | 9.68 ± 1.95 | >200 |
6h | 4-(2-chlorophenyl)piperazin-1-yl | 28.68 ± 11.71 | >200 |
6i | 4-(diphenylmethyl)piperazin-1-yl | 104.98 ± 44.66 | >200 |
6j | pyrrolidin-1-yl | 25.98 ± 8.00 | >200 |
6k | piperidin-1-yl | 27.94 ± 13.79 | >200 |
6l | morpholin-4-yl | 12.62 ± 14.76 | >200 |
Gifitinib | 8.58 ± 1.65 | >200 |
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Ke, J.; Lu, Q.; Wang, X.; Sun, R.; Jin, Z.; Zhan, X.; Hu, J.; Wan, D.C.-c.; Hu, C. Discovery of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors. Molecules 2018, 23, 1980. https://doi.org/10.3390/molecules23081980
Ke J, Lu Q, Wang X, Sun R, Jin Z, Zhan X, Hu J, Wan DC-c, Hu C. Discovery of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors. Molecules. 2018; 23(8):1980. https://doi.org/10.3390/molecules23081980
Chicago/Turabian StyleKe, Jia, Qi Lu, Xin Wang, Rui Sun, Zhe Jin, Xiaoyi Zhan, Jianshu Hu, David Chi-cheong Wan, and Chun Hu. 2018. "Discovery of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors" Molecules 23, no. 8: 1980. https://doi.org/10.3390/molecules23081980
APA StyleKe, J., Lu, Q., Wang, X., Sun, R., Jin, Z., Zhan, X., Hu, J., Wan, D. C.-c., & Hu, C. (2018). Discovery of 4,5-Dihydro-1H-thieno[2′,3′:2,3]thiepino [4,5-c]pyrazole-3-carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for Tyrosine Kinase Inhibitors. Molecules, 23(8), 1980. https://doi.org/10.3390/molecules23081980