Discovery of novel pyrrolo[2, 3-b]pyridine derivatives bearing 1, 2, 3-triazole moiety as c-Met kinase inhibitors. Issue 7 (1st April 2016) - Tang, Qidong
Graphical abstract: 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 compound34 showed excellent in vitro activity. Abstract: 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 analog34 showing a c-Met IC50 value of 1.68 nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X = CF3, R 1 = F, R 2 = 4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.