Format

Send to

Choose Destination
Eur J Med Chem. 2016 Nov 10;123:105-114. doi: 10.1016/j.ejmech.2016.07.040. Epub 2016 Jul 21.

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

Author information

1
BioCIS, Univ. Paris-Sud, CNRS, équipe labellisée Ligue Contre le Cancer, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
2
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.
3
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.

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).

KEYWORDS:

CLK1; DYRK1A; Imidazo[1,2-a]pyridines; Kinase inhibitors

PMID:
27474927
DOI:
10.1016/j.ejmech.2016.07.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center