title: Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2.
abstract: 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.
authors.affiliation: Université Bordeaux Segalen, Pharmacochimie, FRE 3396, F-33000 Bordeaux, France. jean.guillon@u-bordeaux2.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rimbault
authors.forename: Stéphane
authors.initials: S
authors.lastname: Moreau
authors.forename: Solène
authors.initials: S
authors.lastname: Savrimoutou
authors.forename: Noël
authors.initials: N
authors.lastname: Pinaud
authors.forename: Sophie
authors.initials: S
authors.lastname: Baratin
authors.forename: Mathieu
authors.initials: M
authors.lastname: Marchivie
authors.forename: Séverine
authors.initials: S
authors.lastname: Roche
authors.forename: Andre
authors.initials: A
authors.lastname: Bollacke
authors.forename: Adali
authors.initials: A
authors.lastname: Pecci
authors.forename: Lautaro
authors.initials: L
authors.lastname: Alvarez
authors.forename: Vanessa
authors.initials: V
authors.lastname: Desplat
authors.forename: Joachim
authors.initials: J
authors.lastname: Jose
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011810:Quinoxalines; C531444:pyrrolo(1,2-a)quinoxaline; D047390:Casein Kinase II
keywords: Antiproliferative activity; Protein kinase CK2; Pyrrolo[1,2-a]quinoxaline; Synthesis