Design, synthesis and biological evaluation of novel 2-hydroxy-1 H-indene-1,3(2 H)-dione derivatives as FGFR1 inhibitors

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We synthesised a novel series of FGFR1 inhibitors bearing quinoline, quinoxalin and isoquinoline using a synthetic strategy employing a one pot reaction, yielding 2-hydroxy-1 H -indene-1,3(2 H )-dione. Structural elucidation via IR, NMR and HRMS analyses is complemented by a proposed mechanistic pathway. All newly-synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR-1. The most potent derivatives were 9a, 9b, 9c and 7b with IC 50 = 5.7, 3.3, 4.1 and 3.1 μM, respectively, supported by molecular docking studies which probed the binding interactions of these compounds within the active site of the kinase.