(1R,5S)-3-((1S,4R)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyloxy)-8-oxa-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester | 192460-67-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1R,5S)-3-((1S,4R)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyloxy)-8-oxa-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester
• 英文别名: methyl (1R,5S)-3-[(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl]oxy-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate
• CAS: 192460-67-6
• 化学式: C₁₉H₂₄O₇
• 分子量: 364.395
• InChiKey: SQRIBOXAOFHEBD-XJSVZPCESA-N

物化性质

• 沸点：
  507.6±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,5S)-3-((1S,4R)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyloxy)-8-oxa-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.33h， 以94%的产率得到methyl (1R,2R,5S)-3-oxo-8-oxabicyclo[3.2.1]octane-2-carboxylate
  参考文献：
  名称：

  2-Carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes:  Potent Non-Nitrogen Inhibitors of Monoamine Transporters

  摘要：

  Cocaine is a potent stimulant of the mammalian central nervous system. Its reinforcing and stimulant properties have been associated with its propensity to bind to monoamine transporter systems. It has generally been assumed t;hat the amino function on monoamines is a requirement for binding to monoamine transporters. In particular, the 8-amino function on the tropane skeleton of cocaine and cocaine analogs has been assumed to provide an ionic bond to the aspartic acid residue on the dopamine transporter(DAT). We have prepared the first 8-oxa analogs of the 3-aryltropanes (WIN compounds) and have found that the 3 beta-(3,4-dichlorophenyl) (6g) and 3 alpha-(3,4-dichlorophenyl) (7g) analogs are particularly potent (IC50 = 3.27 and 2.34 nM, respectively) inhibitors of the dopamine transporter. We now describe the synthesis and biology of the family of 2-carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes and demonstrate that an amino nitrogen is not required for binding to the DAT.

  DOI：

  10.1021/jm9703045
• 作为产物：
  描述：

  (1S)-(-)-莰烷酰氯 、 2-carbomethoxy-8-oxabicyclo[3.2.1]octanone 以 四氢呋喃 为溶剂， 生成 (1R,5S)-3-((1S,4R)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyloxy)-8-oxa-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Tropane analogs and methods for inhibition of monoamine transport

  摘要：

  描述了与单胺转运体结合的新型托烷类似物，特别是具有6-或7-取代基的8-氮杂、8-碳和8-氧托烷。本发明的化合物可以是外消旋混合物、纯R-对映异构体或纯S-对映异构体。本发明中某些优选的化合物对DAT（多巴胺转运体）与SERT（血清素转运体）的选择性较高。还描述了包含以药用可接受载体配制的化合物的药物治疗组合物，以及通过接触单胺转运体以本发明中的化合物的5-羟基色氨酸再摄取抑制量来抑制5-羟基色氨酸再摄取的方法。用于本发明实施的首选单胺转运体包括多巴胺转运体、血清素转运体和去甲肾上腺素转运体。

  公开号：

  US06353105B1

文献信息

• Tropane analogs and methods for inhibition of monoamine transport
  申请人：Organix, Inc.

  公开号：US06353105B1

  公开（公告）日：2002-03-05

  New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.

  描述了与单胺转运体结合的新型托烷类似物，特别是具有6-或7-取代基的8-氮杂、8-碳和8-氧托烷。本发明的化合物可以是外消旋混合物、纯R-对映异构体或纯S-对映异构体。本发明中某些优选的化合物对DAT（多巴胺转运体）与SERT（血清素转运体）的选择性较高。还描述了包含以药用可接受载体配制的化合物的药物治疗组合物，以及通过接触单胺转运体以本发明中的化合物的5-羟基色氨酸再摄取抑制量来抑制5-羟基色氨酸再摄取的方法。用于本发明实施的首选单胺转运体包括多巴胺转运体、血清素转运体和去甲肾上腺素转运体。
• 2-Carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes:  Potent Non-Nitrogen Inhibitors of Monoamine Transporters
  作者：Peter C. Meltzer、Anna Y. Liang、Paul Blundell、Mario D. Gonzalez、Zhengming Chen、Clifford George、Bertha K. Madras

  DOI：10.1021/jm9703045

  日期：1997.8.1

  Cocaine is a potent stimulant of the mammalian central nervous system. Its reinforcing and stimulant properties have been associated with its propensity to bind to monoamine transporter systems. It has generally been assumed t;hat the amino function on monoamines is a requirement for binding to monoamine transporters. In particular, the 8-amino function on the tropane skeleton of cocaine and cocaine analogs has been assumed to provide an ionic bond to the aspartic acid residue on the dopamine transporter(DAT). We have prepared the first 8-oxa analogs of the 3-aryltropanes (WIN compounds) and have found that the 3 beta-(3,4-dichlorophenyl) (6g) and 3 alpha-(3,4-dichlorophenyl) (7g) analogs are particularly potent (IC50 = 3.27 and 2.34 nM, respectively) inhibitors of the dopamine transporter. We now describe the synthesis and biology of the family of 2-carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes and demonstrate that an amino nitrogen is not required for binding to the DAT.