Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC(50 )value of 0.012 mu M) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC(50 )values of 0.64 mu M, 1.92 mu M and 2.68 mu M, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

Automated summary

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their antitumor activities. The results showed that most of the compounds exhibited moderate to good antitumor activities. Compound T14 demonstrated the most promising antiproliferative activities against three cancer cell lines.