Objective: A series of novel 2,4-diaminosubstituted pyrrolo[3,2-d]pyrimidines was synthesized
together with their corresponding 7-phenyl or 7-isopropyl counterparts.
Results: Among the target derivatives, the 7-substituted analogues exhibited interesting cytotoxic activity against
a panel of PI3Kα related human breast cancer cell lines, namely MCF7, T47D, MDA-MB-231 and HCC1954.
Selected compounds were tested for potential PI3Kα inhibitory activity as well as for their cytotoxic effect in
prostate cancer cell lines (DU145 and PC3).
Conclusion: Derivatives bearing a specific substitution pattern consisting of 7-phenyl as well as a 2-(4-
aminocyclohexylamino) moiety (16c, 16f) display kinase inhibitory activity, elucidated on the basis of molecular
simulation studies, which revealed their interaction with the DFG motif of the kinase.