New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia

•Design and synthesis of new 2,6,9-trisubstituted purine derivatives.•Compounds 5c and 5d were potent inhibitors of both kinases, with IC50 values of 40 nM and 0.58/0.66 μM for Abl and Btk, respectively.•Structural requirements for Bcr-Abl and Btk inhibition were analyzed with docking and 3D-QSAR.•5c and 5d could suppress the proliferation of leukemia and lymphoma cells at low micromolar concentrations in vitro.•5c inhibited the downstream signaling of both kinases in the respective cell models.