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]

Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01086026
Contributor : Muriel Cadieu <>
Submitted on : Friday, November 21, 2014 - 4:17:27 PM
Last modification on : Wednesday, December 9, 2020 - 3:10:41 PM
Long-term archiving on: : Monday, February 23, 2015 - 9:07:46 AM

Synthesis of new pyridazino_ac...

Files produced by the author(s)

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

File

Identifiers

Collections

Citation

Export

Metrics

451

442

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

File

Identifiers

Collections

Citation

Export

Share

Metrics

451

442