(1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-(6-amino-hexylcarbamoyl)-pentyl ester | 843660-60-6

• 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-(6-amino-hexylcarbamoyl)-pentyl ester
• CAS: 843660-60-6
• 化学式: C₂₈H₄₃N₃O₅
• 分子量: 501.667
• InChiKey: XBDTUWBWVRFHDJ-CONSUNNSSA-N

物化性质

• 沸点：
  662.9±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  36.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  110.96
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Fluorescein isothiocyanate 、 (1R,2R,3S,5S)-3-Benzoyloxy-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 5-(6-amino-hexylcarbamoyl)-pentyl ester 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 以78.4 mg的产率得到5-[6-[6-[(1R,2R,3S,5S)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl]oxyhexanoylamino]hexylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid
  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：

  芽子碱盐酸盐 在 palladium on activated charcoal 1-ethyl-4-dimethylaminoethylcarbodiimide 、 四甲基氢氧化铵 、 四乙基碘化铵 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 30.5h， 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