Theoretical study of disubstituted pyrrolopyrimidines as focal Adhesion Kinase inhibitors

摘要

An in silico molecular modeling study of selected 7H-pyrrolo[2,3-d] pyrimidines with FAK inhibitory activities was performed. Rigid docking of each inhibitor at the FAK catalytic site was employed to obtain the most appropriate starting structures, followed by molecular mechanics-based energy minimizations associated with molecular dynamics at the FAK binding site using the AMBER force field. Theoretical values of interaction energies obtained from the geometry optimization calculations for the protein-inhibitor complexes were compared with published IC _(50) values for FAK and showed a reasonable correlation. Based on these results and in view of the geometry of the most potent inhibitors, two new molecular structures were designed as possible FAK inhibitors and submitted to the same theoretical procedures.