Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs

In silico based design and synthesis of non-nucleosidic DOT1L inhibitors is presented. SAR led to the identification of key moieties. The compounds were evaluated on related epigenetic targets and μM-range potency hit inhibitors were identified.