2941-78-8Relevant articles and documents
Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease
Yao, Hong,Uras, Giuseppe,Zhang, Pengfei,Xu, Shengtao,Yin, Ying,Liu, Jie,Qin, Shuai,Li, Xinuo,Allen, Stephanie,Bai, Renren,Gong, Qi,Zhang, Haiyan,Zhu, Zheying,Xu, Jinyi
, p. 7483 - 7506 (2021/06/28)
Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
Synthetic method of 2-amino-4-bromo-N,5-dimethyl benzamide
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Paragraph 0005; 0006; 0007, (2017/04/27)
The invention discloses a synthetic method of 2-amino-4-bromo-N,5-dimethyl benzamide, and belongs to the field of chemical synthesis. The synthetic method comprises the following steps: firstly, by taking 2-nitro-5-methyl benzoic acid as a raw material and using ferric chloride hexahydrate and palladium as a composite catalyst, adding the materials into hydrazine hydrate solution and performing reduction reaction to obtain 2-amino-5-methyl benzoic acid; adding the 2-amino-5-methyl benzoic acid and dichloromethane into bis(trichloromethyl) carbonate tetrahydrofuran solution by taking pyridine as a catalyst, and performing cyclization reaction; after the reaction is ended, performing microwave heating to reflux; after reflux, adding methylamine water solution and performing amination reaction to obtain 2-amino-N,5-dimethyl benzamide; finally, enabling the 2-amino-N,5-dimethyl formamide, hydrogen peroxide and hydrobromic acid solution to perform halogenating reaction, thus obtaining the 2-amino-4-bromo-N,5-dimethyl benzamide.
The Synthesis of 5-Amino-dihydrobenzo[b]oxepines and 5-Amino-dihydrobenzo[b]azepines via Ichikawa Rearrangement and Ring-Closing Metathesis
Chwastek, Monika,Pieczykolan, Micha?,Stecko, Sebastian
, p. 9046 - 9074 (2016/10/17)
The combination of Ichikawa's rearrangement and a ring-closing metathesis reaction of allyl carbamates is presented as a method for the preparation of 5-amino-substituted 2,5-dihydro-benzo[b]oxepines, 2,5-dihydro-benzo[b]azepines, and 2,5-dihydro-benzo[b]thiepins. It was demonstrated that the use of nonracemic allyl carbamates enables the synthesis of enantioenriched benzo-fused seven-membered heterocycles. Finally, it was shown that further functionalization of the obtained structures allows access to pharmacologically active 5-amino-substituted 2,3,4,5-tetrahydro-1-benzo[b]oxepine scaffolds.
