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Design, Synthesis and Biological Evaluation of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-Substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors
Zhang, Z.; Zhao, D.; Dai, Y.; Cheng, M.; Geng, M.; Shen, J.; Ma, Y.; Ai, J.; Xiong, B. Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors. Molecules2016, 21, 1407.
Zhang, Z.; Zhao, D.; Dai, Y.; Cheng, M.; Geng, M.; Shen, J.; Ma, Y.; Ai, J.; Xiong, B. Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors. Molecules 2016, 21, 1407.
Zhang, Z.; Zhao, D.; Dai, Y.; Cheng, M.; Geng, M.; Shen, J.; Ma, Y.; Ai, J.; Xiong, B. Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors. Molecules2016, 21, 1407.
Zhang, Z.; Zhao, D.; Dai, Y.; Cheng, M.; Geng, M.; Shen, J.; Ma, Y.; Ai, J.; Xiong, B. Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors. Molecules 2016, 21, 1407.
Abstract
Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.
Chemistry and Materials Science, Medicinal Chemistry
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