1552301-08-2

Upstream product

• 67443-38-3 5-bromo-2-chloro-3-nitropyridine 
• 152684-30-5 5-bromo-2-methoxy-3-nitropyridine 
• 73183-34-3 bis(pinacol)diborane 
• 1083168-94-8 2-methoxy-3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine 
• 893440-50-1 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine 
• 701-27-9 3-fluorobenzene-1-sulfonyl chloride 
• 884495-39-0 5-bromo-2-(methyloxy)-3-pyridinamine 

Downstream Products

• 1552300-77-2 N-(5-(7-amino-1-cyclopentyl-5-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-methoxypyridin-3-yl)-3-fluorobenzenesulfonamide 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel 4-alkynyl-quinoline derivatives as PI3K/mTOR dual inhibitors

Abstract A novel series of 4-alkynyl-quinoline derivatives were designed, synthesized and biologically evaluated for their PI3Kα inhibitory activities and anti-proliferative effects against two cancer cell lines PC-3 and HCT-116. Most of them showed potent PI3Kα inhibitory activities with IC50 values at low nanomolar level and good to excellent anti-proliferative effects against both cell lines. Among them, compound 15d, the most potent one, was selected for further biological evaluation. As a result, 15d displayed strong inhibitory activity against other class I PI3K isoforms (PI3Kβ, PI3Kγ and PI3Kδ) and mTOR with an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that the phosphorylation of Akt, another downstream effector of PI3K, can be remarkably suppressed by 15d at cellular level. All these experimental results suggested that 15d is a potent PI3K/mTOR dual inhibitor and could serve as a promising lead compound for the development of anticancer agents.

Micro-reactor tandem synthesis method of indole anticancer drug molecules

The invention relates to a micro-reactor tandem synthesis method of indole anticancer drug molecules. The method comprises the following steps: a reaction liquid 1 and a reaction liquid 2 are mixed, then are introduced into a first micro-reactor, and are reacted to obtain a first effluent, the first effluent and a reaction liquid 3 are mixed, then are introduced into a second micro-reactor, and are reacted to obtain a second effluent, the second effluent and a reaction liquid 4 are mixed, then are introduced into a third micro-reactor, and are reacted to obtain a final effluent, and the finaleffluent is concentrated and separated to obtain the indole anticancer drug molecules, wherein the reaction liquid 1 is a mixed solution containing 5-bromine-3-amino-2-substituted (R1)-pyridine, the reaction liquid 2 is substituted (R2)-benzenesulfonyl chloride, the reaction liquid 3 is a mixed solution containing bis(pinacolato)diboron, the reaction liquid 4 is a mixed solution containing a 5-bromo-7-azaindole derivative, and the indole anticancer drug molecules are benzenesulfonamidopyridylazaindole compounds. Compared with the prior art, the method of the invention has the advantages of high reaction efficiency, few side reactions and simple production process.

Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K/mTOR

The identification and lead optimization of a series of pyridopyrimidinone derivatives are described as a novel class of efficacious dual PI3K/mTOR inhibitors, resulting in the discovery of 31. Compound 31 exhibited high enzyme activity against PI3K and mTOR, potent suppression of Akt and p70s6k phosphorylation in cell assays, and good pharmacokinetic profile. Furthermore, compound 31 demonstrated in vivo efficacy in a PC-3M tumor xenograft model.