6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3β inhibitors.
The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.
['Uehara|Fumiaki|F|', 'Shoda|Aya|A|', 'Aritomo|Keiichi|K|', 'Fukunaga|Kenji|K|', 'Watanabe|Kazutoshi|K|', 'Ando|Ryoichi|R|', 'Shinoda|Masaki|M|', 'Ueno|Hiroaki|H|', 'Kubodera|Hideo|H|', 'Sunada|Shinji|S|', 'Saito|Ken-Ichi|K|', 'Kaji|Takahide|T|', 'Asano|Shoichi|S|', 'Eguchi|Jun-ichi|J|', 'Yuki|Satoshi|S|', 'Tanaka|Shinji|S|', 'Yoneyama|Yukimi|Y|', 'Niwa|Takuro|T|']
D001665:Binding Sites D004789:Enzyme Activation D038362:Glycogen Synthase Kinase 3 D000071679:Glycogen Synthase Kinase 3 beta D062105:Molecular Docking Simulation D011485:Protein Binding D047428:Protein Kinase Inhibitors D017434:Protein Structure, Tertiary D011744:Pyrimidinones D013329:Structure-Activity Relationship
Alzheimer’s disease Glycogen synthase kinase 3β Hyperphoshorylation Pyrimidin-4(3H)-one Tau protein