Xia, Yuehan published the artcileDiscovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists, Formula: C7H8BClO2, the publication is European Journal of Medicinal Chemistry (2021), 113013, database is CAplus and MEDLINE.
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 I was identified as a weak RORγt agonist during inhouse library screening. Changes in LHS core of I led to the identification of tetrahydroquinoline compound II as a partial RORγt agonist (maximum 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 III (EC50 = 8.9 ± 0.4 nM, maximum act. = 104.5%) and benzomorpholine compound IV (EC50 = 7.5 ± 0.6 nM, maximum 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 III; 59.4% activation at 300 nM of IV). The binding modes of III and IV as well as the two RORγt inverse agonists accidentally discovered were also discussed.
European Journal of Medicinal Chemistry published new progress about 145349-62-8. 145349-62-8 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Boronic Acids, name is 2-Chloro-4-methylphenylboronic acid, and the molecular formula is C13H11NO, Formula: C7H8BClO2.
Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics