Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2-a]pyridines derivatives as protein kinase inhibitors
| Autor: | Mouad Alami, Jean-Daniel Brion, Blandine Baratte, Marie Lawson, Claire Delehouzé, Thomas Robert, Sandrine Ruchaud, Stéphane Bach, Olivier Lozach, Jordi Rodrigo, Abdallah Hamze |
|---|---|
| Přispěvatelé: | Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de criblage d'inhibiteurs de protéines kinases=Kinase Inhibitor Specialized Screening facility (KISSf), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Intégrative (LBI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-11-BTBR-0008,OCEANOMICS,Biotechnologies et bioressources pour la valorisation des écosystèmes marins planctoniques(2011), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Molecular model DYRK1A Imidazo[12-a]pyridines Stereochemistry Pyridines [SDV]Life Sciences [q-bio] CLK1 Protein Serine-Threonine Kinases 01 natural sciences Molecular Docking Simulation 03 medical and health sciences Structure-Activity Relationship Drug Discovery Structure–activity relationship Humans Protein kinase A Protein Kinase Inhibitors Pharmacology 010405 organic chemistry Chemistry Kinase [CHIM.ORGA]Chemical Sciences/Organic chemistry Organic Chemistry General Medicine Protein-Tyrosine Kinases Combinatorial chemistry 0104 chemical sciences 030104 developmental biology Docking (molecular) Kinase inhibitors [CHIM.CHEM]Chemical Sciences/Cheminformatics |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, 2016, 123, pp.105-114. ⟨10.1016/j.ejmech.2016.07.040⟩ |
| ISSN: | 1768-3254 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.07.040⟩ |
| Popis: | International audience; 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 (IC$_{50}$ of 0.7 $\mu$M) and DYRK1A (IC$_{50}$ of 2.6 $\mu$M). |
| Databáze: | OpenAIRE |
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