Formula: C6H2BrF2NO2On September 15, 2020 ,《Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists》 was published in European Journal of Medicinal Chemistry. The article was written by Sun, Nannan; Huang, Yafei; Yu, Mingcheng; Zhao, Yunpeng; Chen, Ji-An; Zhu, Chenyu; Song, Meiqi; Guo, Huimin; Xie, Qiong; Wang, Yonghui. The article contains the following contents:
GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i(I) showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76% inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model. In addition to this study using 2-Bromo-1,3-difluoro-5-nitrobenzene, there are many other studies that have used 2-Bromo-1,3-difluoro-5-nitrobenzene(cas: 886762-62-5Formula: C6H2BrF2NO2) was used in this study.
2-Bromo-1,3-difluoro-5-nitrobenzene(cas: 886762-62-5) belongs to organobromine compounds.Organobromine chemicals are produced naturally by an array of biological and other chemical processes in our environment. Some of these compounds are identical to man-made organobromine compounds, such as methyl bromide, bromoform, and bromophenols, but many others are entirely new moleclar entities, often possessing extraordinary and important biological properties. Formula: C6H2BrF2NO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary