Preprint Article Version 1 NOT YET PEER-REVIEWED

Design, Synthesis and Biological Evaluation of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-Substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

1
Key Laboratory of Structure‐Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China
2
Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
3
Division of Anti‐tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
Version 1 : Received: 29 September 2016 / Approved: 29 September 2016 / Online: 29 September 2016 (15:42:08 CEST)

A peer-reviewed article of this Preprint also exists.

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. Molecules 2016, 21, 1407.

Journal reference: Molecules 2016, 21, 1407
DOI: 10.3390/molecules21101407

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.

Subject Areas

Cancer; FGFR; Inhibitor; 4‐Substituted‐1H‐indazole

Readers' Comments and Ratings (0)

Discuss and rate this article
Views 202
Downloads 179
Comments 0
Metrics 0
Discuss and rate this article

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.