title: Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines.
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.
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Ostrynska
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Anatoliy O
authors.initials: AO
authors.lastname: Balanda
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.affiliation: Otava Ltd, 400 Applewood Crescent, Unit 100, Vaughan, Ontario L4K 0C3, Canada.
authors.forename: Andriy G
authors.initials: AG
authors.lastname: Golub
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Kotey
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Olexander P
authors.initials: OP
authors.lastname: Kukharenko
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Andrii A
authors.initials: AA
authors.lastname: Gryshchenko
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine.
authors.forename: Nadiia V
authors.initials: NV
authors.lastname: Briukhovetska
authors.affiliation: Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., 03680 Kyiv, Ukraine. Electronic address: sergiy@yarmoluk.org.ua.
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000612782:4-aminothieno(2,3-d)pyrimidine; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D047390:Casein Kinase II
keywords: Aminothieno[2,3-d]pyrimidine; Docking; Drug design; Inhibitor; Intramolecular hydrogen bond; Protein kinase CK2