Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors

Amélie Bruel; Romain Bénéteau; Mylène Chabanne; Olivier Lozach; Rémy Le Guevel; Myriam Ravache; Hélène Bénédetti; Laurent Meijer; Cédric Logé; Jean-Michel Robert

doi:10.1016/j.bmcl.2014.09.017

Journal articles

Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors

Amélie Bruel ¹ Romain Bénéteau ¹ Mylène Chabanne ¹ Olivier Lozach ² Rémy Le Guevel ³ Myriam Ravache ³ Hélène Bénédetti ⁴ Laurent Meijer ^{5, 2} Cédric Logé ^{1, *} Jean-Michel Robert ¹

* Corresponding author

1 IICiMed - Cibles et médicaments de l'infection, de l'immunité et du cancer

2 P3H - Phophorylation de protéines et Pathologies Humaines

3 GFAS - Génétique fonctionnelle, agronomie et santé [IFR 140]

4 CBM - Centre de biophysique moléculaire

5 ManRos Therapeutics

Abstract : New pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs were synthesized and their inhibitory activities against DYRK1A, CDK5/p25, GSK3α/β and p110-α isoform of PI3K evaluated using harmine as reference. Both furan-2-yl 10 and pyridin-4-yl 19 from the two different series, exhibited submicromolar IC50 against DYRK1A with no activities against the three other kinases. In addition, compound 10 exhibited antiproliferative activities in the Huh-7, Caco2 and MDA-MB-231 cell lines.

Keywords : Pyridazin-3(2H)-one DYRK1A inhibitors Anti-proliferative effects Synthesis 4-dihydro-5H-pyridazino[4 5-b]indole 4-Oxo-3

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology / Biomolecules [q-bio.BM]

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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01086026
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Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors

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