496-12-8Relevant articles and documents
C2 Symmetric amines. III. An asymmetric synthesis of (S,S)-1,3-dialkyl isoindolines by sequential formamidine alkylation
Meyers,Santiago, Braulio
, p. 5877 - 5880 (1995)
Metalation-alkylation of isoindoline 5 in the form of its chiral formamidine, 6 leads to C2-dialkylated derivatives in high ee's.
Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
, (2020/12/04)
The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
Metal-Free Synthesis of Polycyclic Quinazolinones Enabled by a (NH4)2S2O8-Promoted Intramolecular Oxidative Cyclization
Xie, Lijuan,Lu, Cong,Jing, Dong,Ou, Xinrui,Zheng, Ke
supporting information, p. 3649 - 3653 (2019/06/04)
An efficient metal-free, (NH4)2S2O8 mediated intramolecular oxidative cyclization for the construction of polycyclic heterocycles was disclosed. A series of polycyclic quinazolinone derivatives with good functional group tolerance were obtained in high yields. The natural products tryptanthrin and rutaecarpine, as well as their derivatives, were easily synthesized by this strategy. A preliminary mechanism study suggested the carbon-centered radical was involved in the catalytic cycle.
