Cell Penetrant Inhibitors Of The Kdm4 And Kdm5 Families Of Histone Lysine Demethylases. 2. Pyrido[3,4-D]Pyrimidin-4(3h)-One Derivatives

Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDMSC biochemical and target-specific, cellular mechanistic assays.