N-t-Butoxycarbonyl-O,O-dipivaloyldopamin | 67302-25-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: N-t-Butoxycarbonyl-O,O-dipivaloyldopamin
• CAS: 67302-25-4
• 化学式: C₂₃H₃₅NO₆
• 分子量: 421.534
• InChiKey: XBVIMWGHMPQTIO-UHFFFAOYSA-N

物化性质

• 沸点：
  508.6±50.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  90.93
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-t-Butoxycarbonyl-O,O-dipivaloyldopamin 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide
  参考文献：
  名称：

  Brain-Specific Delivery of Dopamine Mediated by N,N-Dimethyl Amino Group for the Treatment of Parkinson’s Disease

  摘要：

  Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.

  DOI：

  10.1021/mp500352p
• 作为产物：
  描述：

  N-(tert-butoxycarbonyl)dopamine 、 三甲基乙酰氯 以 四氢呋喃 为溶剂， 生成 N-t-Butoxycarbonyl-O,O-dipivaloyldopamin
  参考文献：
  名称：

  Brain-Specific Delivery of Dopamine Mediated by N,N-Dimethyl Amino Group for the Treatment of Parkinson’s Disease

  摘要：

  Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.

  DOI：

  10.1021/mp500352p