22014-99-9Relevant articles and documents
Regioselective 2-alkylation of indoles with α-bromo esters catalyzed by Pd/P,P=O system
Tian, Wei,Li, Bowen,Tian, Duanshuai,Tang, Wenjun
supporting information, p. 197 - 200 (2021/08/13)
A palladium-catalyzed 2-alkylation of indoles with α-bromo esters is developed by employing a P,P=O ligand. The method features excellent regioselectivities, mild reaction conditions, and good functional group compatibility. The employment of the P,P=O ligand as well as 4? molecular sieves were crucial for the success of the transformation. Mechanistic studies indicate the reaction proceed through a radical pathway.
Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors
Chen, Zhe-Sheng,Dai, Qing-Qing,Li, Guo-Bo,Liu, Hong-Min,Liu, Hui,Wang, Bo,Wang, Shaomeng,Yu, Bin,Yuan, Shuo,Zhang, Jing-Ya,Zhang, Xiao-Nan,Zuo, Jia-Hui
, p. 14895 - 14911 (2021/10/12)
The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.
Manganese-Catalyzed Regioselective Dehydrogenative C-versus N-Alkylation Enabled by a Solvent Switch: Experiment and Computation
Borghs, Jannik C.,Zubar, Viktoriia,Zubar, Viktoriia,Azofra, Luis Miguel,Sklyaruk, Jan,Rueping, Magnus,Rueping, Magnus
supporting information, p. 4222 - 4227 (2020/06/04)
The first base metal-catalyzed regioselective dehydrogenative alkylation of indolines using readily available alcohols as the alkylating reagent is reported. A single air-and moisture-stable manganese catalyst provides access to either C3-or N-alkylated indoles depending on the solvent used. Mechanistic studies indicate that the reaction takes place through a combined acceptorless dehydrogenation and hydrogen autotransfer strategy.
