Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors

A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68 nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X = CF3, R1 = F, R2 = 4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.

A series of pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety (18–45) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound 34 showed excellent in vitro activity.Figure optionsDownload as PowerPoint slide