Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties

Author(s): Junjun Zhao, Shaohua Gou*, Xiaobing Zhang, Yan Liang, Lei Fang*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 17 , Issue 8 , 2017

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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.

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Article Details

VOLUME: 17
ISSUE: 8
Year: 2017
Page: [1102 - 1112]
Pages: 11
DOI: 10.2174/1871520616666161031142619
Price: $58

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