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

Autor: Golub AG; 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, Bdzhola VG, Briukhovetska NV, Balanda AO, Kukharenko OP, Kotey IM, Ostrynska OV, Yarmoluk SM
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2011 Mar; Vol. 46 (3), pp. 870-6. Date of Electronic Publication: 2011 Jan 09.
DOI: 10.1016/j.ejmech.2010.12.025
Abstrakt: 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.
(Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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