Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2.
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.
['Guillon|Jean|J|', 'Le Borgne|Marc|M|', 'Rimbault|Charlotte|C|', 'Moreau|Stéphane|S|', 'Savrimoutou|Solène|S|', 'Pinaud|Noël|N|', 'Baratin|Sophie|S|', 'Marchivie|Mathieu|M|', 'Roche|Séverine|S|', 'Bollacke|Andre|A|', 'Pecci|Adali|A|', 'Alvarez|Lautaro|L|', 'Desplat|Vanessa|V|', 'Jose|Joachim|J|']
D047390:Casein Kinase II D004305:Dose-Response Relationship, Drug D006801:Humans D008958:Models, Molecular D015394:Molecular Structure D047428:Protein Kinase Inhibitors D011758:Pyrroles D011810:Quinoxalines D013329:Structure-Activity Relationship
Synthesis Pyrrolo[1,2-a]quinoxaline Protein kinase CK2 Antiproliferative activity