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Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2-a]pyridines derivatives as protein kinase inhibitors

21/07/2016
European Journal of Medicinal Chemistry
123 pp. 105-114

Type

Article dans des revues

Auteurs

Lawson Marie
Rodrigo Jordi
Baratte Blandine
Robert Thomas
Delehouzé Claire
Lozach Olivier
Ruchaud Sandrine
Bach Stéphane
Brion Jean-Daniel
Alami Mouad
Hamze Abdallah

We report here the synthesis, the biological evaluation and the molecular modeling studies of new imidazo[1,2-µ]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 microM) and DYRK1A (IC50 of 2.6 microM)