(1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-carboxy-pentyl ester | 173443-27-1

• 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)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-carboxy-pentyl ester
• 英文别名: O-benzoylecgonine 5-carboxypentyl ester；6-[(1R,2R,3S,5S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl]oxyhexanoic acid
• CAS: 173443-27-1
• 化学式: C₂₂H₂₉NO₆
• 分子量: 403.475
• InChiKey: SORJFXHTZLIBBZ-HLNWXESRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-carboxy-pentyl ester 在 1-ethyl-4-dimethylaminoethylcarbodiimide 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-(6-amino-hexylcarbamoyl)-pentyl ester
  参考文献：
  名称：

  Fluorescent Cocaine Probes:  A Tool for the Selection and Engineering of Therapeutic Antibodies

  摘要：

  Cocaine is a highly addictive drug, and despite intensive efforts, effective therapies for cocaine craving and addiction remain elusive. In recent years, we and others have reported advances in anticocaine immunopharmacotherapy based on specific antibodies capable of sequestering the drug before it reaches the brain. In an effort to obtain high affinity therapeutic anti-cocaine antibodies, either whole IgGs or other antibody constructs, fluorescence spectroscopic techniques could provide a means of assisting selection and engineering strategies. We report the synthesis of a series of cocaine-fluorophore conjugates (GNC-F1, GNC-F2, GNC-I) and the functional evaluation of these compounds against single-chain Fv antibodies obtained via crystallographic analysis/engineering and against commercially available anti-cocaine monoclonal antibodies with a wide range of cocaine-binding affinities. From these studies, we determined that the GNC-F2 fluorophore reproduced affinity constants obtained using [H-3]-labeled cocaine. We anticipate that the readily synthesized and nonradioactive GNC-F2 will find use both as a tool for bioimaging and in the high-throughput selection and engineering of potential therapeutic antibodies against cocaine.

  DOI：

  10.1021/ja043935e
• 作为产物：
  描述：

  古卡因 在 palladium 10% on activated carbon 、 水 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 24.0h， 生成 (1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-carboxy-pentyl ester
  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。
• Fluorescent Cocaine Probes:  A Tool for the Selection and Engineering of Therapeutic Antibodies
  作者：Michael M. Meijler、Gunnar F. Kaufmann、Longwu Qi、Jenny M. Mee、Avery R. Coyle、Jason A. Moss、Peter Wirsching、Masayuki Matsushita、Kim D. Janda

  DOI：10.1021/ja043935e

  日期：2005.3.1

  Cocaine is a highly addictive drug, and despite intensive efforts, effective therapies for cocaine craving and addiction remain elusive. In recent years, we and others have reported advances in anticocaine immunopharmacotherapy based on specific antibodies capable of sequestering the drug before it reaches the brain. In an effort to obtain high affinity therapeutic anti-cocaine antibodies, either whole IgGs or other antibody constructs, fluorescence spectroscopic techniques could provide a means of assisting selection and engineering strategies. We report the synthesis of a series of cocaine-fluorophore conjugates (GNC-F1, GNC-F2, GNC-I) and the functional evaluation of these compounds against single-chain Fv antibodies obtained via crystallographic analysis/engineering and against commercially available anti-cocaine monoclonal antibodies with a wide range of cocaine-binding affinities. From these studies, we determined that the GNC-F2 fluorophore reproduced affinity constants obtained using [H-3]-labeled cocaine. We anticipate that the readily synthesized and nonradioactive GNC-F2 will find use both as a tool for bioimaging and in the high-throughput selection and engineering of potential therapeutic antibodies against cocaine.