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