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ID: ALA2086312

Journal: Eur J Med Chem

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

Authors: Bruel A, Logé C, Tauzia ML, Ravache M, Le Guevel R, Guillouzo C, Lohier JF, Oliveira Santos JS, Lozach O, Meijer L, Ruchaud S, Bénédetti H, Robert JM.

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.

CiteXplore: 23063566

DOI: 10.1016/j.ejmech.2012.09.001