N-acetyl-2 (di-O-acetyl-3,4 phenyl)-3 alanine | 47302-76-1

• 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-acetyl-2 (di-O-acetyl-3,4 phenyl)-3 alanine
• 英文别名: (2S)-2-acetamido-3-(3,4-diacetyloxyphenyl)propanoic acid
• CAS: 47302-76-1
• 化学式: C₁₅H₁₇NO₇
• 分子量: 323.302
• InChiKey: MLXVBDQEYBNZNQ-LBPRGKRZSA-N

物化性质

• 沸点：
  547.7±50.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-acetyl-2 (di-O-acetyl-3,4 phenyl)-3 alanine 在 三乙醇胺 、 氯甲酸异丁酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Molecular mechanism underlying the cerebral effect of Gly-Pro-Glu tripeptide bound to l-dopa in a Parkinson’s animal model

  摘要：

  Oxidative stress is a critical contributing factor to neurodegenerative disorders. Therefore, the inhibition of ROS formation, responsible for chronic detrimental neuroinflammation, is an important strategy for preventing the neurodegenerative disease and for neuroprotective therapy. Gly-Pro-Glu (GPE) is the N-terminal tripeptide of insulin-like growth factor-I, which is naturally cleaved in the plasma and brain tissues. GPE has neuroprotective effects since it crosses the blood-CSF and the functional CSF-brain barriers and binds to glial cells. It has been shown that GPE improves motor behaviour in rats after 6-OHDA lesion, although it does not rescue dopaminergic neurons. Thus, we hypothesized that the GPE therapeutic efficacy in a Parkinson model might be improved by combining GPE to l-dopa. Here, we used an animal model that represents a progressive chronic Parkinson's disease (PD) model, characterized by high levels of oxidative stress and inflammation. We showed that the co-drug, in which l-dopa is covalently linked to the GPE tripeptide, by down-regulating the expression of inflammatory genes, decreases the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inflammatory response and, by up-regulating tyrosine hydroxylase, reduces MPTP-induced neurotoxicity. Furthermore, by determining the nuclear translocation/activation of Nrf2 and NF-kappa B, we showed that systemic administration of the co-drug activates Nrf2-induced antioxidant response while suppressing NF-kappa B inflammatory pathway. Data suggest that the binding of l-dopa to GPE tripeptide might represent a promising strategy to supply l-dopa to parkinsonian patients.

  DOI：

  10.1007/s00726-011-1210-x
• 作为产物：
  描述：

  左旋多巴 、 乙酰氯 以 溶剂黄146 为溶剂， 以2.75 g的产率得到chlorhydrate de (di-O-acetyl-3,4 phenyl)-3 alanine
  参考文献：
  名称：

  Chavis; Grodenic; Imbach, European Journal of Medicinal Chemistry, 1981, vol. 16, # 3, p. 219 - 227

  摘要：

  DOI：

文献信息

• New L‐Dopa Codrugs as Potential Antiparkinson Agents
  作者：Piera Sozio、Antonio Iannitelli、Laura Serafina Cerasa、Ivana Cacciatore、Catia Cornacchia、Gianfabio Giorgioni、Massimo Ricciutelli、Cinzia Nasuti、Franco Cantalamessa、Antonio Di Stefano

  DOI：10.1002/ardp.200700228

  日期：2008.7

  This paper reports the synthesis and preliminary evaluation of new L‐dopa (LD) conjugates (1 and 2) obtained by joining LD with two different natural antioxidants, caffeic acid and carnosine, respectively. The antioxidant efficacy of compounds 1 and 2 was assessed by evaluating plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the rat. Rat striatal concentration

  本文报告了通过将 LD 分别与两种不同的天然抗氧化剂咖啡酸和肌肽结合而获得的新型左旋多巴 (LD) 缀合物（1 和 2）的合成和初步评估。通过评估大鼠中超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GPx) 的血浆活性来评估化合物 1 和 2 的抗氧化功效。在口服联合药物 1 和 2 后，评估了大鼠纹状体 LD 和多巴胺 (DA) 的浓度以及中枢神经效应。结果表明，虽然我们的联合药物缺乏显着的抗氧化活性，但它们能够诱导持续递送大鼠纹状体中的 DA 并能改善大脑中 LD 和 DA 的释放。