Li, Shan; Si, Hongfei; Song, Xiaojuan; Lei, Chong; He, Xiaoqiang; Wang, Jie; Liu, Yiling; Zhou, Yang; Song, Jian-Guo; Peng, Lijie; Tang, Xia; Chan, Shingpan; Ren, Xiaomei; Tu, Zhengchao; Li, Zhengqiu; Wang, Zhen; Zhang, Zhang; Ding, Ke published their research in Journal of Medicinal Chemistry on August 11 ,2022. The article was titled 《Discovery of Hexahydrofuro[3,2-b]furans as New Kinase-Selective and Orally Bioavailable JAK3 Inhibitors for the Treatment of Leukemia Harboring a JAK3 Activating Mutant》.Application of 350-30-1 The article contains the following contents:
Janus kinase 3 (JAK3) is a potential target for the treatment of hematol. malignancies. Herein, we report the discovery of a series of new orally bioavailable irreversible JAK3 kinase inhibitors. The representative compound 12n (I) potently inhibited JAK3 kinase activity with an IC50 value of 1.2 nM and was more than 900-fold selective over JAK1, JAK2, and Tyk2. Cell-based assays revealed that 12n significantly suppressed phosphorylation of JAK3 and the downstream effectors STAT3/5 and also robustly restrained proliferation of BaF3 cells transfected with JAK3M511I activating mutation and human leukemia U937 cells harboring JAK3M511I with IC50 values of 22.9 and 20.2 nM, resp. More importantly, 12n showed reasonable pharmacokinetic (PK) properties, and oral administration of 12n at a dose of 50 mg/kg twice daily led to tumor regression in a U937 cell inoculated xenograft mouse model. Thus, 12n represents a promising lead compound for further optimization to discover new therapeutic agents for hematol. malignancies. In addition to this study using 3-Chloro-4-fluoronitrobenzene, there are many other studies that have used 3-Chloro-4-fluoronitrobenzene(cas: 350-30-1Application of 350-30-1) was used in this study.
3-Chloro-4-fluoronitrobenzene(cas: 350-30-1) belongs to organochlorine compounds. Alkanes and aryl alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Application of 350-30-1
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics