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Design of dual GSK-3β/AChE inhibitors 5 and 6. Tacrine has been extensively used to develop MTDLs by linking a structure responsible for inducing a second biological effect. In the cases reported in the figure, GSK-3β inhibitor 4 has been coupled to tacrine to obtain compound 5 by taking advantage of the amide in 4 localized in solvent-exposed portion of the molecule. In the second example, to obtain compound 6, the structure of valmerin has been used as GSK-3β binding-fragment.
