Figure 1.

Design strategy of dual GSK-3β/AChE inhibitors. (A) Design of a merged GSK-3β/AChE pharmacophore taking advantage of the solvent exposed sites in GSK-3β and the probable interactions to be gained by a merged tacrine at the entrance to AChE substrate binding pocket. (B) X-ray cocrystal structure of 1 in the kinase domain of GSK-3β. Intermolecular interactions are shown as dotted lines with different colors according to the type of the interaction: green, conventional hydrophobic contact; dark pink, π–π stacked; light pink, π-alkyl contact. The thiazolyl methoxy and the primary amide moiety extend into the solvent-exposed region of the protein (red circle).