Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

Abstract

Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment.

• Authors: Yifei Yang, Yuan Zhang, LingYun Yang, Leilei Zhao, Lianghui Si, Huibin Zhang, Qingsong Liu, Jinpei Zhou
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 70 Pg. 126-132 (02 2017) ISSN: 1090-2120 [Electronic] United States
• PMID: 28043720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents
• Imidazoles
• Pyridines
• MET protein, human
• Proto-Oncogene Proteins c-met

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Imidazoles (chemical synthesis, chemistry, pharmacology)
• Molecular Docking Simulation
• Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-met (antagonists & inhibitors, metabolism)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship