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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
- Source :
- Molecules, Vol 21, Iss 10, p 1407 (2016)
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
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-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.
- Subjects :
- cancer
FGFR
inhibitor
4-substituted-1H-indazole
Organic chemistry
QD241-441
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 21
- Issue :
- 10
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8ba2d64d24534ffbb847f4b155da1b11
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules21101407