Next Article in Journal
New 2-Oxoindolin Phosphonates as Novel Agents to Treat Cancer: A Green Synthesis and Molecular Modeling
Next Article in Special Issue
Design, Synthesis, and Antimicrobial Evaluation of Novel Pyrazoles and Pyrazolyl 1,3,4-Thiadiazine Derivatives
Previous Article in Journal
Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells
Previous Article in Special Issue
Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(8), 1980; https://doi.org/10.3390/molecules23081980

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

1
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
2
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Wolfgang Holzer
Received: 30 April 2018 / Revised: 25 June 2018 / Accepted: 17 July 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Pyrazole Derivatives)
Full-Text   |   PDF [1463 KB, uploaded 8 August 2018]   |  

Abstract

The epidermal growth factor receptors (EGFRs), in which overexpression (known as upregulation) or overactivity have been associated with a number of cancers, has become an attractive molecular target for the treatment of selective cancers. We report here the design and synthesis of a novel series of 4,5-dihydro-1H-thieno [2′,3′:2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives and the screening for their inhibitory activity on the EGFR high-expressing human A549 cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). A Docking simulation was performed to fit compound 6g and gifitinib into the EGFR to determine the probable binding models, and the binding sites and modes conformation of 6g and gifitinib were exactly similar, the two compounds were stabilized by hydrogen bond interactions with MET769. Combining with the biological activity evaluation, compound 6g demonstrated the most potent inhibitory activity (IC50 = 9.68 ± 1.95 μmol·L–1 for A549). Conclusively, 4,5-dihydro-1H-thieno[2′,3′:2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives as the EGFR tyrosine kinase inhibitors were discovered, and could be used as potential lead compounds against cancer cells. View Full-Text
Keywords: heterocycle; synthesis; EGFR; tyrosine kinase inhibitor heterocycle; synthesis; EGFR; tyrosine kinase inhibitor
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Ke, J.; Lu, Q.; Wang, X.; Sun, R.; Jin, Z.; Zhan, X.; Hu, J.; Wan, D. .-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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top