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
; 57: 225-33, 2012 Nov.
Article
in En
| MEDLINE
| ID: mdl-23063566
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridazines
/
Protein Kinase Inhibitors
/
Phosphoinositide-3 Kinase Inhibitors
/
Indoles
/
Antineoplastic Agents
Language:
En
Journal:
Eur J Med Chem
Year:
2012
Document type:
Article
Affiliation country:
Francia