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Discovery and Evaluation of Enantiopure 9H-pyrimido[4,5-b]indoles as Nanomolar GSK-3β Inhibitors with Improved Metabolic Stability

Andreev, Stanislav ; Pantsar, Tatu ; El-Gokha, Ahmed ; Ansideri, Francesco ; Kudolo, Mark ; Anton, Débora Bublitz ; Sita, Giulia ; Romasco, Jenny ; Geibel, Christian ; Lämmerhofer, Michael ; Goettert, Márcia Ines ; Tarozzi, Andrea ; Laufer, Stefan A. ; Koch, Pierre


Glycogen synthase kinase-3 beta (GSK-3 beta) is a potential target in the field of Alzheimer's disease drug discovery. We recently reported a new class of 9H-pyrimido[4,5-b]indole-based GSK-3 beta inhibitors, of which 3-(3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)piperidin-1-yl)propanenitrile (1) demonstrated promising inhibitory potency. However, this compound underwent rapid ...


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