Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2.

Jean Guillon, Marc Le Borgne, Charlotte Rimbault, Stéphane Moreau, Solène Savrimoutou, Noël Pinaud, Sophie Baratin, Mathieu Marchivie, Séverine Roche, Andre Bollacke, Adali Pecci, Lautaro Alvarez, Vanessa Desplat, Joachim Jose
European Journal of Medicinal Chemistry. 2013-07-01; 65: 205-222
DOI: 10.1016/j.ejmech.2013.04.051

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Herein we describe the synthesis and properties of substituted
phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class
of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was
designed and synthesized using convenient and straightforward synthesis
protocols. The compounds were tested for inhibition of human protein kinase CK2,
which is a potential drug target for many diseases including inflammatory
disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar
range were identified. The most promising compound, the
4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited
human CK2 with an IC50 of 49 nM. Our findings indicate that
pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further
development and optimization of human protein kinase CK2 inhibitors.

Copyright © 2013 Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.ejmech.2013.04.051
PMID: 23711832 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus