1201844-49-6

Upstream product

• 887309-87-7 N-(5-bromo-2-chloro-pyridine-3-yl)-4-fluorobenzenesulfonamide 
• 24036-52-0 6-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-one 
• 349-88-2 4-Fluorobenzenesulfonyl chloride 
• 588729-99-1 3-amino-5-bromo-2-chloropyridine 
• 1112983-31-9 N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 

Relevant academic research and scientific papers

Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors

PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of molecules with skeleton of 4-phenyl-2H-benzo[b] [1,4]oxazin-3(4H)-one were designed and synthesized targeting this pathway. Bioassays showed that, among all the molecules, 8d-1 was a pan-class I PI3K/mTOR inhibitor with an IC50 of 0.63 nM against PI3Kα. In a wide panel of protein kinases assays, no off-target interactions of 8d-1 were identified. 8d-1 was orally available, and displayed favorable pharmacokinetic parameters in mice (oral bioavailability of 24.1%). In addition, 8d-1 demonstrated significant efficiency in Hela/A549 tumor xenograft models (TGI of 87.7% at dose of 50 mg/kg in Hela model) without causing significant weight loss and toxicity during 30 days treatment. Based on the bioassays, compound 8d-1 could be used as an anti-cancer drug candidate.

INHIBITORS OF PI3 KINASE

The present invention relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein Q, X1, X2, R1 and Z are as defined herein.