Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives

In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin‐2(1H)‐one derivative, exhibited an IC50 value comparable to that of the drug imatinib against c‐Src kinase, and another compound (14) containing a 2‐((4‐methyl‐2‐oxo‐2H‐chromen‐6‐yl)oxy)acetamide demonstrated an IC50 value of 8.39 μM. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single‐crystal X‐ray diffraction technique. These results may serve as a gateway for developing novel next‐generation kinase inhibitors. Building on the pyridylpyrimidinylaminophenyl scaffold, the active pharmacophore of imatinib, various heterocyclic acids were conjugated and a small library of amides was synthesized. The kinase inhibitory potential of the synthesized amides was evaluated against Abl1 and c‐Src. Two compounds, 14 and 20, showed IC50 values of 2.67 and 8.39 µM against the kinase Abl1.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research