- Pyridone hexa-alkyne amine modified derivative and preparation method and application thereof
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The invention relates to a pyridone hexa-alkyne amine modified derivative as shown in a formula (I) and a pharmaceutically acceptable salt thereof, a preparation method thereof, application of the pyridone hexa-alkyne amine modified derivative or the pharmaceutically acceptable salt thereof to preparation of drugs for preventing or treating related diseases, especially Alzheimer's disease and Parkinson's disease, by inhibiting monoamine oxidase, chelating metal iron ions, resisting Abeta and resisting oxidation. According to the invention, a series of novel single-molecule multi-target anti-ADactive compounds are synthesized, and pyridone derivatives with iron ion chelating activity and propynylamine with MAOB inhibitory activity are creatively and organically combined together, so that the compounds have remarkable advantages on Alzheimer's disease with complex pathogenesis; and the combined molecules are far superior to CP20 (deferiprone) in the aspect of iron ion chelating activity.
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Paragraph 0112-0114
(2021/03/30)
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- N-Propargylamine-hydroxypyridinone hybrids as multitarget agents for the treatment of Alzheimer's disease
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AD is a progressive brain disorder. Because of the lack of remarkable single-target drugs against neurodegenerative disorders, the multitarget-directed ligand strategy has received attention as a promising therapeutic approach. Herein, we rationally designed twenty-nine hybrids of N-propargylamine-hydroxypyridinone. The designed hybrids possessed excellent iron-chelating activity (pFe3+ = 17.09–22.02) and potent monoamine oxidase B inhibitory effects. Various biological evaluations of the optimal compound 6b were performed step by step, including inhibition screening of monoamine oxidase (hMAO-B IC50 = 0.083 ± 0.001 μM, hMAO-A IC50 = 6.11 ± 0.08 μM; SI = 73.5), prediction of blood–brain barrier permeability and mouse behavioral research. All of these favorable results proved that the N-propargylamine-hydroxypyridinone scaffold is a promising structure for the discovery of multitargeted ligands for AD therapy.
- Guo, Jianan,Zhang, Yujia,Zhang, Changjun,Yao, Chuansheng,Zhang, Jingqi,Jiang, Xiaoying,Zhong, Zhichao,Ge, Jiamin,Zhou, Tao,Bai, Renren,Xie, Yuanyuan
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- Non-Noble-Metal Metal-Organic-Framework-Catalyzed Carboxylative Cyclization of Propargylic Amines with Atmospheric Carbon Dioxide under Ambient Conditions
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The coupling reaction of propargylic amines and carbon dioxide (CO2) to synthesize 2-oxazolidinones is an important reaction in industrial production, and yet harsh reaction conditions and noble-metal catalysts are often required to achieve high product yields. Herein, one novel noble-metal-free three-dimensional framework, [Mg3Cu2I2(IN)4(HCOO)2(DEF)4]n (1), assembled by magnesium and copper clusters was synthesized and applied to this reaction. Compound 1 displays excellent solvent stability. Importantly, 1, acting as heterogeneous catalyst, can highly catalyze the cyclization of propargylic amines with CO2 under atmospheric pressure at room temperature, which can be recycled at least five times without an obvious decrease of the catalytic activity. NMR spectroscopy, coupled with 13C-isotope- and deuterium-labeling experiments, clearly clarifies the mechanism of this catalytic system: CO2 was successfully captured and converted to the product of 2-oxazolidinones, the CC bond of propargylic amines can be effectively activated by 1, and proton transfer was involved in the reaction process. Density functional theory calculations are further conducted to uncover the reaction path and the crucial role of compound 1 during the reaction.
- Gu, Ai-Ling,Wang, Wan-Ting,Cheng, Xin-Yu,Hu, Tian-Ding,Wu, Zhi-Lei
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supporting information
p. 13425 - 13433
(2021/08/30)
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- Efficient Conversion of Tertiary Propargylamides into Imidazoles via Hydroamination-Cyclization
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A method to convert tertiary N -propargylamides into 1,2,4-trisubstituted imidazoles using ammonium chloride and zinc triflate as the catalyst is reported. The method is convenient, practical and employs conventional heating. It is also applicable to N -propargyl lactams and tends to populate the so-called 'lead-like' chemistry space.
- Safrygin, Alexander,Krivosheyeva, Elena,Dar'in, Dmitry,Krasavin, Mikhail
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p. 3048 - 3058
(2018/07/02)
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