Journal
MOLECULES
Volume 21, Issue 10, Pages -Publisher
MDPI AG
DOI: 10.3390/molecules21101407
Keywords
cancer; FGFR; inhibitor; 4-substituted-1H-indazole
Funding
- Foundation of China Postdoctoral Science Grant [2015M580370]
- National Natural Science Foundation of China [81473243]
- Youth Innovation Promotion Association
- Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020317]
- program for Innovative Research Team of the Ministry of Education
- Program for Liaoning Innovative Research Team in University
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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 newseries of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)N-(3-(4-methylpiperazin-1-yl) phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC50 value of about 30.2 nM.
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