Preprint Article Version 1 NOT YET PEER-REVIEWED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

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