Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and -Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents.

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives - and - containing 4-(morpholinomethyl)phenyl and -substituted benzamides have been designed and synthesized. Among them, compound displayed potent anti-FAK activity (IC = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC = 0.044 ± 0.011 μM) and A431 cells (IC = 0.119 ± 0.036 μM). Furthermore, compound also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound was performed to elucidate its possible binding modes with FAK. These results established as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.