title: Synthesis and biological evaluation of N-aryl-7-methoxybenzo[b]furo[3,2-d]pyrimidin-4-amines and their N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amine analogues as dual inhibitors of CLK1 and DYRK1A kinases.
abstract: Novel N-aryl-7-methoxybenzo[b]furo[3,2-d]pyrimidin-4-amines (1) and their N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amine analogues (2) were designed and prepared for the first time via microwave-accelerated multi-step synthesis. Various anilines were condensed with N'-(2-cyanaryl)-N,N-dimethylformimidamide intermediates obtained by reaction of 3-amino-6-methoxybenzofuran-2-carbonitrile (3) and 3-amino-6-methoxybenzothiophene-2-carbonitrile (4) precursors with dimethylformamide dimethylacetal. The inhibitory potency of the final products against five protein kinases (CDK5/p25, CK1δ/ε, GSK3α/β, DYRK1A and CLK1) was estimated. Compounds (2a-z) turned out to be particularly promising for the development of new pharmacological dual inhibitors of CLK1 and DYRK1A kinases.
authors.affiliation: Université de Rouen, Laboratoire de Chimie Organique et Bio-organique, Réactivité et Analyse (C.O.B.R.A.), CNRS UMR 6014 & FR3038, Institut de Recherche en Chimie Organique Fine (I.R.C.O.F.) 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: 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: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000097603:Dyrk Kinases
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D005663:Furans; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011743:Pyrimidines; D013876:Thiophenes; D000097603:Dyrk Kinases; C066780:Clk dual-specificity kinases