220769-85-7Relevant academic research and scientific papers
Synthesis of N-methylpyridine-chlorofuranformamide analogs as novel OPG up-regulators and inhibitors of RANKL-induced osteoclastogenesis
Liu, Chao,Li, Yining,Sheng, Ren,Han, Xiaowan,Bao, Li,Wang, Chenyin,Wang, Weizhi,Jiang, Xinhai,Han, Jiangxue,Lei, Lijuan,Li, Ni,Zhang, Jing,Chen, Minghua,Li, Yan,Wu, Yexiang,Li, Shunwang,Ren, Yu,Xu, Yanni,Si, Shuyi
, (2021/09/28)
The OPG/RANKL/RANK pathway is a promising target for the design of therapeutic agents used in the treatment of osteoporosis. E09241 with an N-methylpyridine-chlorofuranformamide structural skeleton was previously identified to decrease bone loss and thus protect against osteoporosis in ovariectomized rats through increasing osteoprotegerin (OPG) expression. In this study, 36 derivatives of E09241 (3a) were prepared. The synthesis, up-regulation of OPG activities, SAR (structure–activity relationship), and cytotoxicity of these compounds are presented. Compounds with good up-regulating OPG activities could inhibit RANKL (the receptor activator of nuclear factor-kappa B ligand)-induced osteoclastogenesis in RAW264.7 cells. Particularly, compounds 3c and 3i1 significantly reduced NFATc1 and MMP-9 protein expression through inhibition of the NF-κB and MAPK pathways in RANKL induced RAW264.7 cells. In addition, compounds 3c and 3v significantly promoted osteoblast differentiation in MC3T3-E1 cells in osteogenic medium, and compounds 3c, 3v, and 3i1 obviously increased OPG protein expression and secretion in MC3T3-E1 cells. Furthermore, the pharmacokinetic profiles, acute toxicity, and hERG K+ channel effects of compounds 3a, 3c, 3e, 3v, and 3i1 were investigated. Taken together, these results indicate that N-methylpyridine-chlorofuranformamide analog 3i1 could serve as a promising lead for the development of new agents for treating osteoporosis.
Preparation method of ionic liquid and application of ionic liquid in cyclohexanone synthesis
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Paragraph 0024-0026; 0029-0031, (2020/11/02)
The invention discloses a preparation method of ionic liquid and application of the ionic liquid in cyclohexanone synthesis, and relates to the technical field of organic synthesis. A novel ionic liquid is prepared, the ionic liquid is applied to synthesis of cyclohexanone from cyclohexanol, and the reaction activity is improved by utilizing the catalytic action of the ionic liquid, the reactionspeed is accelerated, the conversion rate of cyclohexanol is improved, and the conversion rate reaches 100%. Also, the ionic liquid is high in catalytic selectivity, so that the generation of by-products can be remarkably reduced, the selectivity of cyclohexanone is improved, and the selectivity reaches 98% or above; meanwhile, water is used as a reaction solvent by utilizing the water solubilityof cyclohexanone and the ionic liquid, so that the environmental friendliness of the preparation process can be enhanced, and the preparation process is suitable for industrial production.
