1. Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines.
- Author
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Ostrynska OV, Balanda AO, Bdzhola VG, Golub AG, Kotey IM, Kukharenko OP, Gryshchenko AA, Briukhovetska NV, and Yarmoluk SM
- Subjects
- Casein Kinase II metabolism, Dose-Response Relationship, Drug, Humans, Models, Molecular, Molecular Structure, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyrimidines chemical synthesis, Pyrimidines chemistry, Structure-Activity Relationship, Casein Kinase II antagonists & inhibitors, Drug Design, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology
- Abstract
An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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