3,4-bis(pivaloyloxy)dopamine | 48198-89-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 3,4-bis(pivaloyloxy)dopamine
• 英文别名: BPD；O,O-Dipivaloyldopamin；(3,4-dipivaloyloxy)phenethylamine；[4-(2-Aminoethyl)-2-(2,2-dimethylpropanoyloxy)phenyl] 2,2-dimethylpropanoate
• CAS: 48198-89-6
• 化学式: C₁₈H₂₇NO₄
• 分子量: 321.417
• InChiKey: YERQWGUWIPSYAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-bis(pivaloyloxy)dopamine 在 pig liver esterase 作用下， 以 水 为溶剂， 反应 0.25h， 生成 多巴胺
  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-benzyloxycarbonyl-3,4-dihydroxyphenylethylamine 在 4-二甲氨基吡啶 、 三氟乙酸 作用下， 以 吡啶 为溶剂， 反应 5.0h， 生成 3,4-bis(pivaloyloxy)dopamine
  参考文献：
  名称：

  Casagrande; Santangelo; Saini, Arzneimittel-Forschung/Drug Research, 1986, vol. 36, # 2 A, p. 291 - 303

  摘要：

  DOI：

文献信息

• [EN] ACETYLATED PRODRUGS FOR DELIVERY ACROSS THE BLOOD-BRAIN BARRIER<br/>[FR] PROMÉDICAMENTS ACÉTYLÉS POUR ADMINISTRATION À TRAVERS LA BARRIÈRE HÉMATO-ENCÉPHALIQUE
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2019204808A1

  公开（公告）日：2019-10-24

  The present disclosure relates to pharmaceutical compositions including a compound derived from a parent compound having a hydroxyl or amino moiety, wherein the hydroxyl in the parent compound is presented as an ester in the compound or the amino in the parent compound is presented as an amide in the compound, and their use to prevent or treat neurological disease.

  本公开涉及包括从具有羟基或氨基团的母化合物衍生的化合物的制药组合物，其中母化合物中的羟基在化合物中呈酯形式，或母化合物中的氨基在化合物中呈酰胺形式，并且它们的用途是预防或治疗神经系统疾病。
• BRAIN-SPECIFIC ANALOGUES OF CENTRALLY ACTING AMINES
  申请人：UNIVERSITY OF FLORIDA

  公开号：EP0174342A1

  公开（公告）日：1986-03-19
• Percutaneously absorbable pharmaceutical preparation containing dopamine derivative
  申请人：SANSHO CO., LTD.

  公开号：EP0431942B1

  公开（公告）日：1994-03-23
• ACETYLATED PRODRUGS FOR DELIVERY ACROSS THE BLOOD-BRAIN BARRIER
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US20210238124A1

  公开（公告）日：2021-08-05

  The present disclosure relates to pharmaceutical compositions including a compound derived from a parent compound having a hydroxyl or amino moiety, wherein the hydroxyl in the parent compound is presented as an ester in the compound or the amino in the parent compound is presented as an amide in the compound, and their use to prevent or treat neurological disease.
• US4771059A
  申请人：——

  公开号：US4771059A

  公开（公告）日：1988-09-13