Abstract
Aims: Total twenty-nine [1,2,4]triazolo[4,3-a]pyrazine derivatives were designed and synthesized.
Method: The target compounds, especially 4aa, showed potent activity to inhibit c-Met both in an enzyme assay and a cellular assay. The comprehensive screening for the inhibition of 60 different kinases revealed that 4aa could selectively inhibit c-Met while had no effect on other kinases, indicating 4aa is an excellent c-Met selective inhibitor. Result: The flow cytometry studies found that 4aa had a similar behavior to the positive control SGX-523 in terms of causing the tumor cell apoptosis and blocking cell-cycle progression. More importantly, 4aa showed much better pharmacokinetic properties than SGX-523. Altogether, the findings suggested the target compounds may be potential anti-tumor drug candidates.Keywords: Antitumor, c-Met inhibitors, selectivity, pharmacokinetic properties, [1, 2, 4] Triazol [4, 3-a] pyridine derivatives, apoptosis.
Anti-Cancer Agents in Medicinal Chemistry
Title:Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties
Volume: 17 Issue: 8
Author(s): Junjun Zhao, Shaohua Gou*, Xiaobing Zhang, Yan Liang and Lei Fang*
Affiliation:
- Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189,China
- Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189,China
Keywords: Antitumor, c-Met inhibitors, selectivity, pharmacokinetic properties, [1, 2, 4] Triazol [4, 3-a] pyridine derivatives, apoptosis.
Abstract: Aims: Total twenty-nine [1,2,4]triazolo[4,3-a]pyrazine derivatives were designed and synthesized.
Method: The target compounds, especially 4aa, showed potent activity to inhibit c-Met both in an enzyme assay and a cellular assay. The comprehensive screening for the inhibition of 60 different kinases revealed that 4aa could selectively inhibit c-Met while had no effect on other kinases, indicating 4aa is an excellent c-Met selective inhibitor. Result: The flow cytometry studies found that 4aa had a similar behavior to the positive control SGX-523 in terms of causing the tumor cell apoptosis and blocking cell-cycle progression. More importantly, 4aa showed much better pharmacokinetic properties than SGX-523. Altogether, the findings suggested the target compounds may be potential anti-tumor drug candidates.Export Options
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Cite this article as:
Zhao Junjun, Gou Shaohua*, Zhang Xiaobing, Liang Yan and Fang Lei*, Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1871520616666161031142619
DOI https://dx.doi.org/10.2174/1871520616666161031142619 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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