title: Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors.
abstract: A useful and rapid access to libraries of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues was designed and optimized for the first time via microwave-accelerated condensation and Dimroth rearrangement of the starting anilines with N'-(2-cyanoaryl)-N,N-dimethylformimidamides obtained by reaction of thiophene precursors with dimethylformamide dimethylacetal. The inhibitory potency of the final products against five protein kinases (CDK5/p25, CK1δ/ɛ, GSK3α/β, DYRK1A and CLK1) was estimated. N-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine series of compounds (4a-j) turned out to be particularly promising for the development of new pharmacological inhibitors of CK1 and CLK1 kinases.
authors.affiliation: Université de Rouen, Laboratoire de Chimie Organique et Bio-organique, Réactivité et Analyse, CNRS UMR 6014 & FR3038, Institut de Recherche en Chimie Organique Fine rue Tesnière, 76130 Mont Saint-Aignan, France.
authors.forename: Yvonnick
authors.initials: Y
authors.lastname: Loidreau
authors.forename: Pascal
authors.initials: P
authors.lastname: Marchand
authors.forename: Carole
authors.initials: C
authors.lastname: Dubouilh-Benard
authors.forename: Marie-Renée
authors.initials: MR
authors.lastname: Nourrisson
authors.forename: Muriel
authors.initials: M
authors.lastname: Duflos
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Nadège
authors.initials: N
authors.lastname: Loaëc
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Thierry
authors.initials: T
authors.lastname: Besson
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011728:Pyridones; D011743:Pyrimidines; D013876:Thiophenes; D017346:Protein Serine-Threonine Kinases