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 IC50value 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 IC50value 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.
Department of Chemistry, University of Delhi, Delhi, India.
Priyanka
P
Manchanda
Department of Chemistry, University of Delhi, Delhi, India.
Badri
B
Parshad
Department of Chemistry, University of Delhi, Delhi, India.|Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard (Hamdard University), New Delhi, India.
Amit
A
Kumar
Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, USA.
Rakesh K
RK
Tiwari
Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, USA.
Amir N
AN
Shirazi
Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, USA.
Keykavous
K
Parang
Department of Chemistry, University of Delhi, Delhi, India.
Sunil K
http://orcid.org/0000-0001-7295-0441
SK
Sharma
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000081247:CSK Tyrosine-Protein Kinase; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D047428:Protein Kinase Inhibitors; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
Amide derivatives; Imatinib; Kinase inhibitors; Pyridin-2(1H)-one; Pyridylpyrimidinylaminophenyl