74467-00-8Relevant articles and documents
Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction
Pan, Hongmei,Lu, Tong,Wu, Xuedan,Gu, Chengwen,Tao, Naili,Zhang, Biao,Wang, Ao,Chen, Guangmei,Zhang, Kehua,Cheng, Jie,Jin, Jie
supporting information, p. 2360 - 2364 (2019/11/11)
A novel structure of sinomenine isoxazole derivatives is synthesised from sinomenine hydrochloride and aromatic aldehydes and requires six steps. 19 target compounds have been obtained in good yields. The sinomenine hydrochloride transforms to 4-alkynyl sinomenine, which is a key intermediate product to synthesise the target sinomenine isoxazole compounds, after a neutralisation reaction with ammonia and substitution reaction with 3-chloropropyne. Another key intermediate product is 1,3-dipole, which can be obtained from aromatic aldehyde. After treatment with hydroxylamine hydrochloride and then sodium carbonate solution, aromatic aldehyde is converted to aldehyde oxime, which reacts with N-chlorosuccinimide (NCS) to afford aryl hydroximino chloride. 1,3-Dipole is eventually formed in situ while triethylamine (TEA) in DMF is added dropwise. Then 4-alkynyl sinomenine is added to provide the sinomenine isoxazole derivative via 1,3-dipolar cycloaddition reaction as the key step. All the target compounds are characterised by melting point, 1H NMR, 13C NMR, HRMS and FT-IR spectroscopy.
Design and Structural Optimization of Dual FXR/PPARδActivators
Schierle, Simone,Neumann, Sebastian,Heitel, Pascal,Willems, Sabine,Kaiser, Astrid,Pollinger, Julius,Merk, Daniel
supporting information, p. 8369 - 8379 (2020/08/12)
Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) δhave been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR?-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPARδactivator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPARδand was structurally refined to a potent and balanced FXR/PPARδactivator in a computer-aided fashion. The resulting dual FXR/PPARδmodulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.
SO2F2-Mediated one-pot cascade process for transformation of aldehydes (RCHO) to cyanamides (RNHCN)
Ding, Chengrong,Ge, Shuting,Wei, Junjie,Zhang, Guofu,Zhao, Yiyong
, p. 17288 - 17292 (2020/05/18)
A simple, mild and practical cascade process for the direct conversion of aldehydes to cyanamides was developed featuring a wide substrate scope and great functional group tolerability. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable cyanamides in a pot, atom, and step-economical manner with a green nitrogen source. This protocol will serve as a robust tool for the installation of the cyanamide moiety in various complicated molecules.
