Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core

Abstract Starting from the recently launched FLT3/AXL multi-targeted inhibitor Gilteritinib ( 5 ), we conducted a side-chain ring closure medicinal chemistry approach leading to the identification of compound 15c as a highly potent AXL inhibitor in the biochemical and cellular anti-proliferative assays, with IC 50 values of 1.2 and 0.3 nM, respectively. Compared with the reference compound 5 , our new discovered AXL inhibitor 15c is more potent in both assays.