(1R,2R,3S,5S)-2-((6-(benzyloxy)-6-oxohexyl)carbamoyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,2R,3S,5S)-2-((6-(benzyloxy)-6-oxohexyl)carbamoyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate
• 英文别名: [(1R,2R,3S,5S)-8-methyl-2-[(6-oxo-6-phenylmethoxyhexyl)carbamoyl]-8-azabicyclo[3.2.1]octan-3-yl] benzoate
• 化学式: C₂₉H₃₆N₂O₅
• 分子量: 492.615
• InChiKey: RZAWKWOPRZJYED-ZJMAKVHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,5S)-2-((6-(benzyloxy)-6-oxohexyl)carbamoyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 96.0h， 以89%的产率得到6-((1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxamido)hexanoic acid
  参考文献：
  名称：

  MOLECULES THAT STIMULATE THE IMMUNE SYSTEM FOR TREATMENT OF DRUG ADDICTION, METHODS OF SYNTHESIS, ANTIDRUG VACCINE AND USES

  摘要：

  这项技术涉及用于治疗药物成瘾和滥用的免疫系统刺激分子及其合成过程。这些分子具有杯芳烃化学结构，最好是杯[4]芳烃和/或杯[8]芳烃，与类似于可卡因的半抗原偶联，最好是GNE和/或GNC。还描述了使用这种分子的抗药疫苗，特别是抗可卡因。这种抗药疫苗还可用于预防怀孕妇女使用药物但不希望或无法在怀孕期间停止使用时胎儿暴露于药物。

  公开号：

  US20200385376A1
• 作为产物：
  描述：

  古卡因 在 4-二甲氨基吡啶 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 121.5h， 生成 (1R,2R,3S,5S)-2-((6-(benzyloxy)-6-oxohexyl)carbamoyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate
  参考文献：
  名称：

  MOLECULES THAT STIMULATE THE IMMUNE SYSTEM FOR TREATMENT OF DRUG ADDICTION, METHODS OF SYNTHESIS, ANTIDRUG VACCINE AND USES

  摘要：

  这项技术涉及用于治疗药物成瘾和滥用的免疫系统刺激分子及其合成过程。这些分子具有杯芳烃化学结构，最好是杯[4]芳烃和/或杯[8]芳烃，与类似于可卡因的半抗原偶联，最好是GNE和/或GNC。还描述了使用这种分子的抗药疫苗，特别是抗可卡因。这种抗药疫苗还可用于预防怀孕妇女使用药物但不希望或无法在怀孕期间停止使用时胎儿暴露于药物。

  公开号：

  US20200385376A1

文献信息

• MOLECULES THAT STIMULATE THE IMMUNE SYSTEM FOR TREATMENT OF DRUG ADDICTION, METHODS OF SYNTHESIS, ANTIDRUG VACCINE AND USES
  申请人：UNIVERSIDADE FEDERAL DE MINAS GERAIS

  公开号：US20200385376A1

  公开（公告）日：2020-12-10

  This technology relates to immune system stimulating molecules to be used in the treatment of drug addiction and abuse and their synthesis processes. These molecules have a calixarene chemical structure, preferably calix[4]arene and/or calix[8]arene, coupled to an hapten analogous to cocaine, preferably GNE and/or GNC. An anti-drug vaccine, specifically anti-cocaine, is also described using such molecules. The anti-drug vaccine can be also used to prevent fetal exposure to drugs in pregnant women who use drugs and do not wish or cannot stop their use during pregnancy.

  这项技术涉及用于治疗药物成瘾和滥用的免疫系统刺激分子及其合成过程。这些分子具有杯芳烃化学结构，最好是杯[4]芳烃和/或杯[8]芳烃，与类似于可卡因的半抗原偶联，最好是GNE和/或GNC。还描述了使用这种分子的抗药疫苗，特别是抗可卡因。这种抗药疫苗还可用于预防怀孕妇女使用药物但不希望或无法在怀孕期间停止使用时胎儿暴露于药物。
• Efficient Syntheses of Cocaine Vaccines and Their <i>in Vivo</i> Evaluation
  作者：Atsushi Kimishima、Margaret E. Olson、Yoshihiro Natori、Kim D. Janda

  DOI：10.1021/acsmedchemlett.8b00051

  日期：2018.5.10

  Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clinical trials. As a result, anticocaine vaccines must be further optimized to achieve clinical translation. Herein, we report a study on the relationship between vaccine efficacy and hapten stability toward hydrolysis. Two haptens developed by our laboratory, GND and GNE, were conjugated to tetanus toxoid (TT) and formulated with alum and cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) adjuvants, the optimal formulation in anticocaine vaccine design. GND, a diamide, is more hydrolytically stable than GNE, a monoamide, toward butyrylcholinesterases. Ultimately, both vaccines induced antibodies with high affinity for cocaine. In hyperlocomotion testing, GND-TT and GNE-TT vaccinated mice exhibited a robust blockade of cocaine's stimulatory effects at all tested doses. Overall, antibodies raised against both haptens were highly effective in protecting mice from cocaine-induced psychostimulation.