Xia, Yuehan published the artcileDiscovery of tetrahydroquinolines and benzomorpholines as novel potent ROR¦Ãt agonists, Computed Properties of 104-03-0, the publication is European Journal of Medicinal Chemistry (2021), 113013, database is CAplus and MEDLINE.
The retinoic acid receptor-related orphan receptor ¦Ãt (ROR¦Ãt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). ROR¦Ãt agonists increase basal activity of ROR¦Ãt and could provide a potential approach to cancer immunotherapy. Herein, hit compound I was identified as a weak ROR¦Ãt agonist during inhouse library screening. Changes in LHS core of I led to the identification of tetrahydroquinoline compound II as a partial ROR¦Ãt 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 ROR¦Ãt agonists. Tetrahydroquinoline compound III (EC50 = 8.9 ¡À 0.4 nM, maximum act. = 104.5%) and benzomorpholine compound IV (EC50 = 7.5 ¡À 0.6 nM, maximum act. = 105.8%) were representative compounds with high ROR¦Ãt 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 ROR¦Ãt inverse agonists accidentally discovered were also discussed.
European Journal of Medicinal Chemistry published new progress about 104-03-0. 104-03-0 belongs to catalysis-chemistry, auxiliary class Nitro Compound,Carboxylic acid,Benzene, name is 4-Nitrophenylacetic acid, and the molecular formula is C6H9N3O2S, Computed Properties of 104-03-0.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia