A new α-benzylidene–γ-butyrolactone scaffold was designed and systematically diversified.

Several scaffolds showing selectivity for Dyrk1A, Clk1 and CK2 were identified, with IC₅₀s from the low µM to the nM range.

Multi-targeted kinase inhibitors were also obtained, that co-inhibited the lipid kinases PI3Kα/γ.

Compounds possessing different scaffolds inhibited tau phosphorylation in intact cells.