1334127-69-3Relevant articles and documents
Synthesis and biological evaluation of glycogen synthase kinase 3 (GSK-3) inhibitors: An fast and atom efficient access to 1-aryl-3-benzylureas
Monte, Fabio Lo,Kramer, Thomas,Bol?nder, Alexander,Plotkin, Batya,Eldar-Finkelman, Hagit,Fuertes, Ana,Dominguez, Juan,Schmidt, Boris
, p. 5610 - 5615 (2011/10/09)
The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-3 inhibitor AR-A014418 (AstraZeneca). This moiety suits both (a) a convergent approach utilizing readily accessible building blocks and (b) a divergent approach based on a microwave heating assisted Suzuki coupling. We established a chromatography-free purification method to generate products with sufficient purity for the biological assays. The structure-activity relationship of the library provided the rationale for the synthesis of the benzothiazolylurea 66 (IC50 = 140 nM) and the pyridylurea 62 (IC 50 = 98 nM), which displayed two to threefold enhanced activity versus the reference compound 18 (AR-A014418: IC50 = 330 nM) in our assays.
