Synthesis and Antitumor Activity,Novel 4-Phenoxypyridine Derivatives as Potential c-Met Kinase Inhibitors
To explore new compounds with high c-Met inhibition activity,six novel 4-phenoxypyridine derivatives were synthesized from 4-chloropyridin-2-amine via etherification,acylation,alkylation,reduction and amidation.The compounds obtained were then identified by infrared spectrum,H nuclear magnetic spectrum and mass spectrum,followed by preliminary evaluations on their antitumor activities.The results indicated that all the six target compounds showed antiproliferative activities against MKN-45,A549,H460 and HT-29.Two compounds showed excellent c-Met inhibition activities.Among them,compound 7b exhibited remarkable antiproliferative activities against MKN-45,A549,H460 and HT-29 cell lines with IC50 value of 1.89 μmol/L,5.14 μmol/L,0.74 μmol/L and 0.60 μmol/L,respectively.The inhibitory activities of 7b in the concentration of 1 000 nmol/L and 200 nmol/L against c-Met kinase were 96.2％and 82.8％.These results showed that 7b can serve as a scaffold for further structural optimization and antitumor mechanism studies.
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