(1R-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo<3.2.1>octyl 3-N-(4'-aminophenyl)carbamate | 131013-14-4

• 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-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo<3.2.1>octyl 3-N-(4'-aminophenyl)carbamate
• 英文别名: (1R-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo[3.2.1]octyl 3-N-(4'-aminophenyl)carbamate；methyl (1R,2R,3S,5S)-3-[(4-aminophenyl)carbamoyloxy]-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 131013-14-4
• 化学式: C₁₇H₂₃N₃O₄
• 分子量: 333.387
• InChiKey: CYBZNQQOIMXQCO-LJISPDSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo<3.2.1>octyl 3-N-(4'-aminophenyl)carbamate 在 盐酸 、 sodium azide 、 sodium nitrite 作用下， 生成 (1R,2-exo,3-exo)-3-<oxy>-8-methyl-8-azabicyclo<3.2.1>octane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of Substituted 3-Carbamoylecgonine Methyl Ester Analogs: Irreversible and Photoaffinity Ligands for the Cocaine Receptor/Dopamine Transporter

  摘要：

  Photoaffinity ligands are useful tools for the isolation, purification, and characterization of proteins. As a step toward the goal of producing a photoaffinity probe for the dopamine transporter, isocyanato and azido derivatives of 3-[(phenylcarbamoyl)oxy]ecgonine methyl ester were synthesized and tested for their ability to interact with the cocaine receptor of mammalian brain via two different assays. The ability of two isothiocyanato (N=C=S) (para and meta) and two azido (N-3) (para and meta) derivatives, as well as (-)-cocaine, to inhibit [H-3]cocaine binding and [H-3]dopamine uptake and to covalently interact with the cocaine-binding site was tested. The p-N=C=S was the most potent, with IC50 values of 0.23 and 0.49 mu M for [H-3] cocaine binding and [H-3] dopamine uptake. The m-N-3 and p-N-3 inhibited [3H]cocaine binding with IC50 values of 0.63 and 1.00 mu M and inhibited [H-3] dopamine uptake with IC50 values of 5.08 and 1.32 mu M, respectively. Preincubation of synaptosomal membranes with the m- or p-N=C=S isomer either in reduced lighting or under ultraviolet light followed by two washes resulted in inhibition of 70% and 85% of [3H]cocaine binding, respectively, indicating the highly reactive properties of these compounds. After preincubation in reduced lighting, m-N-3 and p-N-3 inhibited 0% and 13% of [H-3] cocaine binding, while following preincubation under ultraviolet light, the inhibition increased to 61% and 68%, respectively. Thus, the isothiocyanato derivatives appear to bind irreversibly to the cocaine receptor in the presence or absence of ultraviolet light, whereas the azido derivatives are photoreactive compounds which may prove useful in the purification of the receptor.

  DOI：

  10.1021/jm00040a019
• 作为产物：
  描述：

  盐酸古柯碱 在 platinum(IV) oxide 氢气 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 (1R-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo<3.2.1>octyl 3-N-(4'-aminophenyl)carbamate
  参考文献：
  名称：

  合成3-氨基甲酰基芽子碱甲酯类似物作为可卡因结合和多巴胺吸收的抑制剂。

  摘要：

  合成了五个（1R-2-exo-3-exo）-3-（N-苯基氨基甲酰基）芽子碱甲酯类似物，并通过1H和13C NMR，IR和热喷涂MS进行了表征。该化合物分两步或三步以高收率（-56％）从（-）-芽子碱合成为（-）-立体异构体。评估这些可卡因衍生物抑制[3H]可卡因与大鼠纹状体组织结合的能力，以及抑制[3H]多巴胺摄入由同一组织制备的突触小体的能力。最有效的类似物是3-N-（3'-硝基苯基）氨基甲酸酯（1R-2-exo-3-exo）-2-（羰甲氧基）-8-甲基-8-氮杂双环[3.2.1]辛基。抑制可卡因结合和多巴胺摄取的IC50值分别为37和178 nM。氨基衍生物的活性比硝基和（1R-2-exo-3-exo）-2-（羰甲氧基）-8-甲基-8-氮杂双环[3.2.1]辛基3-N-（4'

  DOI：

  10.1021/jm00106a035

文献信息

• KLINE, RICHARD H. (JR);WRIGHT, JEREMY;ESHLEMAN, AMY J.;FOX, KRISTINE M.;E+, J. MED. CHEM., 34,(1991) N, C. 702-705
  作者：KLINE, RICHARD H. (JR)、WRIGHT, JEREMY、ESHLEMAN, AMY J.、FOX, KRISTINE M.、E+

  DOI：——

  日期：——
• Synthesis of 3-carbamoylecgonine methyl ester analogs as inhibitors of cocaine binding and dopamine uptake
  作者：Richard H. Kline、Jeremy Wright、Amy J. Eshleman、Kristine M. Fox、Mohyee E. Eldefrawi

  DOI：10.1021/jm00106a035

  日期：1991.2

  (-)-stereoisomers from (-)-ecgonine in good yield (56% overall). These cocaine derivatives were assessed for their ability to inhibit [3H]cocaine binding to rat striatal tissue and to inhibit [3H]dopamine uptake into synaptosomes prepared from the same tissue. The most potent of the analogues was (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8-azabicyclo[3.2.1]octyl 3-N-(3'-nitrophenyl)carbamate. IC50 values

  合成了五个（1R-2-exo-3-exo）-3-（N-苯基氨基甲酰基）芽子碱甲酯类似物，并通过1H和13C NMR，IR和热喷涂MS进行了表征。该化合物分两步或三步以高收率（-56％）从（-）-芽子碱合成为（-）-立体异构体。评估这些可卡因衍生物抑制[3H]可卡因与大鼠纹状体组织结合的能力，以及抑制[3H]多巴胺摄入由同一组织制备的突触小体的能力。最有效的类似物是3-N-（3'-硝基苯基）氨基甲酸酯（1R-2-exo-3-exo）-2-（羰甲氧基）-8-甲基-8-氮杂双环[3.2.1]辛基。抑制可卡因结合和多巴胺摄取的IC50值分别为37和178 nM。氨基衍生物的活性比硝基和（1R-2-exo-3-exo）-2-（羰甲氧基）-8-甲基-8-氮杂双环[3.2.1]辛基3-N-（4'
• Synthesis of Substituted 3-Carbamoylecgonine Methyl Ester Analogs: Irreversible and Photoaffinity Ligands for the Cocaine Receptor/Dopamine Transporter
  作者：Richard H. Kline、Amy J. Eshleman、Mohyee E. Eldefrawi、Jeremy Wright

  DOI：10.1021/jm00040a019

  日期：1994.7

  Photoaffinity ligands are useful tools for the isolation, purification, and characterization of proteins. As a step toward the goal of producing a photoaffinity probe for the dopamine transporter, isocyanato and azido derivatives of 3-[(phenylcarbamoyl)oxy]ecgonine methyl ester were synthesized and tested for their ability to interact with the cocaine receptor of mammalian brain via two different assays. The ability of two isothiocyanato (N=C=S) (para and meta) and two azido (N-3) (para and meta) derivatives, as well as (-)-cocaine, to inhibit [H-3]cocaine binding and [H-3]dopamine uptake and to covalently interact with the cocaine-binding site was tested. The p-N=C=S was the most potent, with IC50 values of 0.23 and 0.49 mu M for [H-3] cocaine binding and [H-3] dopamine uptake. The m-N-3 and p-N-3 inhibited [3H]cocaine binding with IC50 values of 0.63 and 1.00 mu M and inhibited [H-3] dopamine uptake with IC50 values of 5.08 and 1.32 mu M, respectively. Preincubation of synaptosomal membranes with the m- or p-N=C=S isomer either in reduced lighting or under ultraviolet light followed by two washes resulted in inhibition of 70% and 85% of [3H]cocaine binding, respectively, indicating the highly reactive properties of these compounds. After preincubation in reduced lighting, m-N-3 and p-N-3 inhibited 0% and 13% of [H-3] cocaine binding, while following preincubation under ultraviolet light, the inhibition increased to 61% and 68%, respectively. Thus, the isothiocyanato derivatives appear to bind irreversibly to the cocaine receptor in the presence or absence of ultraviolet light, whereas the azido derivatives are photoreactive compounds which may prove useful in the purification of the receptor.