Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2

被引：58

作者：

Golub, Andriy G. ^{[1
]}

Bdzhola, Volodymyr G. ^{[1
]}

Briukhovetska, Nadiia V. ^{[1
]}

Balanda, Anatoliy O. ^{[1
]}

Kukharenko, Olexander P. ^{[1
]}

Kotey, Igor M. ^{[1
]}

Ostrynska, Olga V. ^{[1
]}

Yarmoluk, Sergiy M. ^{[1
,2
]}

机构：

[1] Natl Acad Sci Ukraine, Inst Mol Biol & Genet, Dept Combinatorial Chem, UA-03143 Kiev, Ukraine

[2] Otava Ltd, UA-03143 Kiev, Ukraine

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 03期

关键词：

Protein kinase CK2; Drug target; Inhibitor; Thienopyrimidine; Docking; Organic synthesis; PHOSPHORYLATION; THIENOPYRIMIDINE; FEATURES; DESIGN;

D O I：

10.1016/j.ejmech.2010.12.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (IC50 values are 0.1 mu M and 0.125 mu M, 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. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：870 / 876

页数：7

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