4-((1R,2R,3S,5S)-3-(((benzyloxy)(phenyl)phosphoryl)oxy)-2-(methoxycarbonyl)-8-azabicyclo[3.2.1]octan-8-yl)-4-oxobutanoic acid trifluoroacetate salt | 1431753-56-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 4-((1R,2R,3S,5S)-3-(((benzyloxy)(phenyl)phosphoryl)oxy)-2-(methoxycarbonyl)-8-azabicyclo[3.2.1]octan-8-yl)-4-oxobutanoic acid trifluoroacetate salt
• 英文别名: 4-[(1R,2R,3S,5S)-2-methoxycarbonyl-3-[phenyl(phenylmethoxy)phosphoryl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-4-oxobutanoic acid;2,2,2-trifluoroacetic acid
• CAS: 1431753-56-8
• 化学式: C₂HF₃O₂*C₂₆H₃₀NO₈P
• 分子量: 629.524
• InChiKey: PEKSHEVQDOOOOJ-ZTFSPWQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.16
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  157
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4-((1R,2R,3S,5S)-3-(((benzyloxy)(phenyl)phosphoryl)oxy)-2-(methoxycarbonyl)-8-azabicyclo[3.2.1]octan-8-yl)-4-oxobutanoic acid trifluoroacetate salt 在 氢气 、 钯 作用下， 以 乙醇 为溶剂， 以85%的产率得到4-((1R,2R,3S,5S)-3-((hydroxy(phenyl)phosphoryl)oxy)-2-(methoxycarbonyl)-8-azabicyclo[3.2.1]octan-8-yl)-4-oxobutanoic acid trifluoroacetate salt
  参考文献：
  名称：

  Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

  摘要：

  Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.

  DOI：

  10.1021/jm400228w
• 作为产物：
  描述：

  (1R,2R,3S,5S)-methyl 3-(((benzyloxy)(phenyl)phosphoryl)oxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate 在 甲酸 、 potassium carbonate 、 三乙胺 、 锌 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 16.67h， 生成 4-((1R,2R,3S,5S)-3-(((benzyloxy)(phenyl)phosphoryl)oxy)-2-(methoxycarbonyl)-8-azabicyclo[3.2.1]octan-8-yl)-4-oxobutanoic acid trifluoroacetate salt
  参考文献：
  名称：

  Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

  摘要：

  Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.

  DOI：

  10.1021/jm400228w

文献信息

• Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design
  作者：Xiaoqing Cai、Timothy Whitfield、Mark S. Hixon、Yanabel Grant、George F. Koob、Kim D. Janda

  DOI：10.1021/jm400228w

  日期：2013.5.9

  Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.