Discovery of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridines as potent anaplastic lymphoma kinase (ALK) inhibitors

  • Bioorg Med Chem Lett. 2019 Apr 1;29(7):912-916. doi: 10.1016/j.bmcl.2019.01.037.
Changwei Chen  1 ,  Peichen Pan  1 ,  Ziyang Deng  1 ,  Dahai Wang  1 ,  Qifan Wu  1 ,  Lei Xu  2 ,  Tingjun Hou  3 ,  Sunliang Cui  4
Affiliations
  • 1. College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China.
  • 2. Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, PR China.
  • 3. College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China. Electronic address: [email protected].
  • 4. College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China. Electronic address: [email protected].
PMID: 30777610 DOI: 10.1016/j.bmcl.2019.01.037
Abstract

A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v against ALK was up to 1.58 nM and a binding mechanism was proposed.

Keywords
1H-pyrazolo[3,4,-b]pyridine; ALK; Anti-tumor; Inhibitor; Kinase.