%0 Journal Article
%T Conformational restriction of a type II FMS inhibitor leading to discovery of 5-methyl-N-(2-aryl-1H-benzo[d]imidazo-5-yl)isoxazole-4-carboxamide analogues as selective FLT3 inhibitors
%A Daseul Im
%A Hyungwoo Moon
%A Jingwoong Kim
%A Jung-Mi Hah
%A Miyoung Jang
%A Youri Oh
%J Journal of Enzyme Inhibition and Medicinal Chemistry
%D 2019
%R https://doi.org/10.1080/14756366.2019.1671837
%X Abstract A series of 4-arylamido 5-methylisoxazole derivatives incorporating benzimidazole was designed and synthesised by conformational restriction of an in-house type II FMS inhibitor. Kinase profiling of one compound revealed interesting features, with increased inhibitory potency towards FLT3 and concomitant loss of potency towards FMS. Several benzimidazole derivatives 5a¨C5g and 6a¨C6c containing various hydrophobic moieties were synthesised, and their inhibitory activity against FLT3 was evaluated. Specifically, 5a, 5-methyl-N-(2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-5-yl) isoxazole-4-carboxamide, exhibited the most potent inhibitory activity against FLT3 (IC50 = 495£¿nM), with excellent selectivity profiles
%U https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1671837