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Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives
Author(s) -
Manchanda Priyanka,
Parshad Badri,
Kumar Amit,
Tiwari Rakesh K.,
Shirazi Amir N.,
Parang Keykavous,
Sharma Sunil K.
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600390
Subject(s) - pharmacophore , chemistry , amide , stereochemistry , ic50 , kinase , amine gas treating , acetamide , combinatorial chemistry , biochemistry , in vitro , organic chemistry
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(1 H )‐one derivative, exhibited an IC 50 value comparable to that of the drug imatinib against c‐Src kinase, and another compound ( 14 ) containing a 2‐((4‐methyl‐2‐oxo‐2 H ‐chromen‐6‐yl)oxy)acetamide demonstrated an IC 50 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.