- Coumarin hybrid pyridinone amide derivative with potential anti-AD activity and preparation method and application of derivative
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The invention discloses a coumarin hybrid pyridinone amide derivative and a preparation method and application thereof. The coumarin hybrid pyridinone amide derivative and pharmacologically acceptablesalt thereof are shown in the formula (I) and the formula (II), and the derivative can be used for preparing drugs for resisting the Alzheimer's disease, the Parkinson's disease or treating other diseases or symptoms by suppressing monoamine oxidase, chelating metallic iron ions, resisting A and resisting oxidation.
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Paragraph 0085; 0087-0089
(2020/02/27)
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- Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity
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A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe3+ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-β1-42 (Aβ1-42) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.
- Bai, Renren,Gu, Jinping,Guo, Jianan,Jiang, Xiaoying,Lv, Yangjing,Mi, Zhisheng,Shi, Yuan,Xie, Yuanyuan,Yao, Chuansheng,Zhang, Changjun,Zhou, Tao
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- Systematic comparison of the mono-, dimethyl-and trimethyl 3-hydroxy-4(1H)-pyridones-Attempted optimization of the orally active iron chelator, deferiprone
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A range of close analogues of deferiprone have been synthesised. The group includes mono-, di-and trimethyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe3+ values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NHcontaining hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis.
- Xie, Yuan-Yuan,Lu, Zidong,Kong, Xiao-Le,Zhou, Tao,Bansal, Sukhi,Hider, Robert
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p. 132 - 140
(2016/04/05)
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- STUDIES TOWARDS 3,4-DIMETHOXY-1-METHYL-1,2-DIHYDROPYRIDINE, SO CALLED ARECOLIDINE, OR ITS TAUTOMERS
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Different synthetic paths towards the title compound (2) lead to intermediates (3, 11, 13, 14, 15, and 17).All of these, but especially 3 and 14 are very close to the target molecule or its tautomers.These, however, turn out to be too unstable for isolation.Thus, the structure of the compound described as arecolidine must be wrong.
- Dehmlow, Eckehard V.,Westerheide, Ralf
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p. 355 - 366
(2007/10/02)
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