1309778-75-3Relevant academic research and scientific papers
Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation
Chen, Yi,Deng, Mingli,Jia, Yu,Ling, Yun,Liu, Xiaofeng,Lu, Mingzhu,Qiu, Tianze,Xiang, Ruiqing,Yang, Chengbin,Yang, Yongtai,Zhou, Yaming
supporting information, (2021/10/19)
Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease
Down, Kenneth,Amour, Augustin,Baldwin, Ian R.,Cooper, Anthony W.J.,Deakin, Angela M.,Felton, Leigh M.,Guntrip, Stephen B.,Hardy, Charlotte,Harrison, Zo? A.,Jones, Katherine L.,Jones, Paul,Keeling, Suzanne E.,Le, Joelle,Livia, Stefano,Lucas, Fiona,Lunniss, Christopher J.,Parr, Nigel J.,Robinson, Ed,Rowland, Paul,Smith, Sarah,Thomas, Daniel A.,Vitulli, Giovanni,Washio, Yoshiaki,Hamblin, J. Nicole
supporting information, p. 7381 - 7399 (2015/10/05)
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
INDAZOLE DERIVATIVES AS PI 3 - KINASE INHIBITORS
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, (2011/06/25)
The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.
