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

Changwei Chen; Peichen Pan; Ziyang Deng; Dahai Wang; Qifan Wu; Lei Xu; Tingjun Hou; Sunliang Cui

doi:10.1016/j.bmcl.2019.01.037

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. Epub 2019 Feb 1.

Authors

Changwei Chen¹, Peichen Pan¹, Ziyang Deng¹, Dahai Wang¹, Qifan Wu¹, Lei Xu², Tingjun Hou³, Sunliang Cui⁴

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: tingjunhou@zju.edu.cn.
⁴ College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China. Electronic address: slcui@zju.edu.cn.

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.

MeSH terms

Anaplastic Lymphoma Kinase / antagonists & inhibitors*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Humans
Protein Binding
Pyridines / chemistry
Pyridines / pharmacology*

Substances

Antineoplastic Agents
Pyridines
ALK protein, human
Anaplastic Lymphoma Kinase