2. Academic Validation
  3. Synthesis and biological evaluation of new 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles as PI3Kα inhibitors

Synthesis and biological evaluation of new 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles as PI3Kα inhibitors

  • Eur J Med Chem. 2012 Nov:57:225-33. doi: 10.1016/j.ejmech.2012.09.001.
Amélie Bruel 1,  Cédric Logé,  Marie-Ludivine de Tauzia,  Myriam Ravache,  Rémy Le Guevel,  Christiane Guillouzo,  Jean-François Lohier,  Jana Sopkova-de Oliveira Santos,  Olivier Lozach,  Laurent Meijer,  Sandrine Ruchaud,  Hélène Bénédetti,  Jean-Michel Robert
Affiliations

Affiliation

  • 1 Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICIMED-EA 1155, UFR Sciences Pharmaceutiques, 1 rue Gaston Veil, Nantes F-44035 Cedex 1, France.
PMID: 23063566 DOI: 10.1016/j.ejmech.2012.09.001
Abstract

A series of novel 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles was synthesized through a newly developed approach. All these compounds were evaluated against DYRK1A, CDK5 and PI3Kα and showed promising inhibitory activities against PI3Kα with most IC(50) values in the micromolar range. Among them, compound 18 was strongly considered as the most interesting compound with an IC(50) value of 0.091 μM. This series exhibited also significant anti-proliferative effects in various human Cancer cell lines including those resulting in activation of the PI3K pathway.

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