N-[4′-hydroxy-3′-methoxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine methyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[4′-hydroxy-3′-methoxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine methyl ester
• 英文别名: N-(4-hydroxy-3-methoxy-E-cinnamoyl)-L-3,4-dihydroxyphenylalanine methyl ester；N-feruloyl-L-DOPA methyl ester；coumaroyl(3-OMe)-Tyr(3-OH)-OMe；methyl (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]propanoate
• 化学式: C₂₀H₂₁NO₇
• 分子量: 387.389
• InChiKey: AJXBUJJCNMFVCM-GPAKFWEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  左旋多巴 在 氯化亚砜 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 N-[4′-hydroxy-3′-methoxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine methyl ester
  参考文献：
  名称：

  具有邻苯二酚功能的氯泛酰胺类似物作为强效帕金森氏病药物的合成和生物学评价

  摘要：

  • 在这项研究中，设计并合成了7种氯仿酰胺类似物（1 – 7），并在SH中评估了1 – 7以及8 – 15（在我们先前的工作中制备）对H 2 O 2诱导的氧化应激的神经保护作用。-SY5Y细胞。结果表明，1 - 7与儿茶酚基团表现出比更好的神经保护作用8 - 15，以及它们的EC 50值从4.26到不等23.83μM，特别是1，表明邻苯二酚的部分支配了这些化合物的活性。此外，口服1（10或20 mg / kg）被证明具有通过减轻体内和体外细胞凋亡和氧化应激以及上调血红素加氧酶-1（HO-1）的表达而具有抗PD的作用。 ）通过PI3K / AKT / mTOR途径进行。最后，在大鼠中确定1的药代动力学（PK）评估。这些发现表明1可能是PD治疗的有效候选者。

  DOI：

  10.1016/j.bmcl.2018.11.030

文献信息

• Synthesis of Lipophilic Clovamide Derivatives and Their Antioxidative Potential against Lipid Peroxidation
  作者：Jakob P. Ley、Heinz-Jürgen Bertram

  DOI：10.1021/jf034286d

  日期：2003.7.1

  Some N-(hydroxycinnamoyl)-L-tyrosine and L-DOPA alkyl esters were synthesized and evaluated as a variation of the clovamide (N-caffeoyl-L-3,4-dihydroxyphenylalanine) structure, a known antioxidant found in red clover. The amides were prepared in good yields starting from methyl and dodecylesters Of L-tyrosine and L-DOPA by reacting with the N-hydroxysuccinimidyl esters of ferulic, sinapic, and acetyl-protected caffeic acid, respectively. In the DPPH. (2,2-diphenyl-1-picrylhydrazyl) and superoxide radical quencher assays they showed radical scavenging activity equal to or higher than those of the standard antioxidants ascorbic acid and tocopherol. The antioxidative potentials of the clovamide derivatives against bulk lipid oxidation, as determined by the accelerated autoxidation of oils, were equal to or higher than those of the standard antioxidants; some of the compounds were able to protect an emulsion of linoleic acid/beta-carotene against oxidation. N-Caffeoyl L-tyrosine methyl ester and the N-cinnamoyl L-DOPA alkyl esters especially were potent antioxidants in bulk lipids and moderate protectants in emulsions.
• Anti-tyrosinase, antioxidant and antimicrobial activities of hydroxycinnamoylamides
  作者：Lyubomir Georgiev、Maya Chochkova、Iskra Totseva、Katya Seizova、Emma Marinova、Galya Ivanova、Mariana Ninova、Hristo Najdenski、Tsenka Milkova

  DOI：10.1007/s00044-012-0419-x

  日期：2013.9

  Synthetic hydroxycinnamoylamides of amino acids (precursors of aromatic amines) were studied for their antioxidant activity in vitro by two antioxidant assay systems, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and inhibition of lipid peroxidation (LPO). Furthermore, these compounds were tested and compared with their corresponding cinnamoylamides of aromatic amines for their inhibitory activity using mushroom tyrosinase. In addition, five hydroxycinnamoyl amino acid amides were investigated for their antimicrobial effect. Structure-activity relationships analysis disclosed that the presence of catechol rest at amino acid or at benzene moieties of substituted cinnamic acid amides significantly scavenged DPPH radical and inhibited LPO. The results obtained by LPO clearly expressed the positive influence of indole moiety on the activity. Moreover, the existence of p-hydroxy substituted cinnamic acid moiety leads to better tyrosinase inhibition. Amongst the tested compounds, amides of p-coumaroyldopamine or tyramine and their corresponding amino acid precursors are the most potent tyrosinase inhibitors.
• Synthesis and biological evaluation of clovamide analogues with catechol functionality as potent Parkinson’s disease agents in vitro and in vivo
  作者：Jia-Hao Feng、Xiao-Long Hu、Xian-Yu Lv、Bao-Lin Wang、Jun Lin、Xiao-Qi Zhang、Wen-Cai Ye、Fei Xiong、Hao Wang

  DOI：10.1016/j.bmcl.2018.11.030

  日期：2019.1

  • In this study, seven clovamide analogues (1–7) were designed and synthesized, and the neuroprotection of 1–7 as well as 8–15 (prepared in our previous work) against H2O2-induced oxidative stress was evaluated in SH-SY5Y cells. Results showed that 1–7 with catechol groups exhibited better neuroprotective effects than 8–15, and their EC50 values ranged from 4.26 to 23.83 μM, especially 1, indicating

  • 在这项研究中，设计并合成了7种氯仿酰胺类似物（1 – 7），并在SH中评估了1 – 7以及8 – 15（在我们先前的工作中制备）对H 2 O 2诱导的氧化应激的神经保护作用。-SY5Y细胞。结果表明，1 - 7与儿茶酚基团表现出比更好的神经保护作用8 - 15，以及它们的EC 50值从4.26到不等23.83μM，特别是1，表明邻苯二酚的部分支配了这些化合物的活性。此外，口服1（10或20 mg / kg）被证明具有通过减轻体内和体外细胞凋亡和氧化应激以及上调血红素加氧酶-1（HO-1）的表达而具有抗PD的作用。 ）通过PI3K / AKT / mTOR途径进行。最后，在大鼠中确定1的药代动力学（PK）评估。这些发现表明1可能是PD治疗的有效候选者。