title: Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2-a]pyridines derivatives as protein kinase inhibitors.
abstract: We report here the synthesis, the biological evaluation and the molecular modeling studies of new imidazo[1,2-a]pyridines derivatives designed as potent kinase inhibitors. This collection was obtained from 2-aminopyridines and 2-bromoacetophenone which afforded final compound in only one step. The bioactivity of this family of new compounds was tested using protein kinase and ATP competition assays. The structure-activity relationship (SAR) revealed that six compounds inhibit DYRK1A and CLK1 at a micromolar range. Docking studies provided possible explanations that correlate with the SAR data. The most active compound 4c inhibits CLK1 (IC50 of 0.7 μM) and DYRK1A (IC50 of 2.6 μM).
authors.affiliation: BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lawson
authors.affiliation: BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodrigo
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Baratte
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Delehouzé
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruchaud
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS USR3151, "Protein Phosphorylation and Human Disease" Unit, Plateforme de criblage KISSf, Station Biologique de Roscoff, Place Georges Teissier, 29688, Roscoff, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.affiliation: BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.affiliation: BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Mouad
authors.initials: M
authors.lastname: Alami
authors.affiliation: BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France. Electronic address: abdallah.hamze@u-psud.fr.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Hamze
mesh_terms: D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097603:Dyrk Kinases
chemical_list: D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D000097603:Dyrk Kinases; C066780:Clk dual-specificity kinases; C001439:imidazo(1,2-a)pyridine
keywords: CLK1; DYRK1A; Imidazo[1,2-a]pyridines; Kinase inhibitors