660867-80-1Relevant articles and documents
Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease
Liu, Wenwu,Liu, Xin,Tian, Liting,Gao, Yaping,Liu, Wenjie,Chen, Huanhua,Jiang, Xiaowen,Xu, Zihua,Ding, Huaiwei,Zhao, Qingchun
, (2021/06/21)
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathology. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biological effects on the prevention of AD. In this study, a new series of harmine derivatives were designed, synthesized and evaluated as dual GSK-3β/DYRK1A inhibitors for their multiple biological activities. The in vitro results indicated that most of them displayed promising activity against GSK-3β and DYRK1A. Among them, compound ZDWX-25 showed potent inhibitory effects on GSK-3β and DYRK1A with IC50 values of 71 and 103 nM, respectively. Molecular modelling and kinetic studies verified that ZDWX-25 could interact with the ATP binding pocket of GSK-3β and DYRK1A. Western blot analysis revealed that ZDWX-25 inhibited hyperphosphorylation of tau protein in okadaic acid (OKA)-induced SH-SY5Y cells. In addition, ZDWX-25 showed good blood-brain barrier penetrability in vitro. More importantly, ZDWX-25 could ameliorate the impaired learning and memory in APP/PS1/Tau transgenic mice. These results indicated that the harmine-based compounds could be served as promising dual-targeted candidates for AD.
Meta-Selective C-H Borylation of Benzamides and Pyridines by an Iridium-Lewis Acid Bifunctional Catalyst
Yang, Lichen,Uemura, Nao,Nakao, Yoshiaki
supporting information, p. 7972 - 7979 (2019/05/22)
We report herein the iridium-catalyzed meta-selective C-H borylation of benzamides by using a newly designed 2,2′-bipyridine (bpy) ligand bearing an alkylaluminum biphenoxide moiety. We also demonstrate the iridium-catalyzed C3-selective C-H borylation of pyridine with a 1,10-phenanthroline (Phen) ligand bearing an alkylborane moiety. It is proposed that the Lewis acid-base interaction between the Lewis acid moiety and the aminocarbonyl group or the sp2-hybridized nitrogen atom accelerates the reaction and controls the site-selectivity.
Design and Synthesis of Tunable Ligands with 4,4′-Bipyridyl as an Electron-Accepting Unit and Their Rhenium Complexes
Kamatsuka, Takuto,Shinokubo, Hiroshi,Miyake, Yoshihiro
supporting information, p. 3429 - 3434 (2017/09/15)
We have designed and prepared a series of rhenium complexes with 4,4′-bipyridyl as an electron-accepting unit. Electrochemical studies revealed that oxidation and reduction of these complexes occurred on the rhenium center and the 4,4′-bipyridyl skeleton, respectively. The redox potentials of the rhenium complexes are controllable by tuning the substituents on the 4,4′-bipyridyl skeleton and the coordinating groups to the rhenium center. We have also examined the reactivity of the rhenium complexes in electrochemical and photochemical CO2 reduction.
