title: Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2.
abstract: A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC(50) values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.
authors.affiliation: Department of Combinatorial Chemistry, Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine,150 Zabolotnogo Street, 03143 Kyiv, Ukraine. andrew.golub@gmail.com
authors.forename: Andriy G
authors.initials: AG
authors.lastname: Golub
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.forename: Nadiia V
authors.initials: NV
authors.lastname: Briukhovetska
authors.forename: Anatoliy O
authors.initials: AO
authors.lastname: Balanda
authors.forename: Olexander P
authors.initials: OP
authors.lastname: Kukharenko
authors.forename: Igor M
authors.initials: IM
authors.lastname: Kotey
authors.forename: Olga V
authors.initials: OV
authors.lastname: Ostrynska
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; 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: D002264:Carboxylic Acids; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C476003:thienopyrimidine; D047390:Casein Kinase II