(1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(3-carboxypropionyloxymethyl)-8-oxabicyclo[3.2.1]octane | 1020108-13-7

• 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-(3,4-dichlorophenyl)-2-(3-carboxypropionyloxymethyl)-8-oxabicyclo[3.2.1]octane
• CAS: 1020108-13-7
• 化学式: C₁₈H₂₀Cl₂O₅
• 分子量: 387.26
• InChiKey: AEFVAVLAHKBLNH-RSUWNVLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,5S)-3-(3,4-dichlorophenyl)-2-hydroxymethyl-8-methyl-8-azabicyclo[3.2.1]octane 、 (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(3-carboxypropionyloxymethyl)-8-oxabicyclo[3.2.1]octane 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.5h， 以79%的产率得到((1R,2S,3S,5S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl)methyl,((1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-oxabicyclo[3.2.1]octan-2-yl)methyl succinate
  参考文献：
  名称：

  The synthesis of bivalent 2β-carbomethoxy-3β-(3,4-dichlorophenyl)-8-heterobicyclo[3.2.1]octanes as probes for proximal binding sites on the dopamine and serotonin transporters

  摘要：

  3-Aryltropanes have been widely explored for potential medications for remediation of cocaine abuse. Research has focused predominantly on 8-azatropanes and it is now well recognized that these compounds can be designed to manifest varied selectivity and potency for inhibition of the dopamine, serotonin, and norepinephrine uptake systems. We had reported that the 8-nitrogen atom present in the 3-aryltropanes is not essential for tropanes to bind to monoamine uptake systems. We demonstrated that compounds in which the amine had been exchanged for an ether or a thioether retained binding potency and selectivity. We have now designed bivalent compounds in which two tropane moieties are linked by an intervening chain. These 8-homo- and 8-heterotropane bivalent compounds allowed a search for adjacent tropane binding sites on the DAT as well as a further exploration of whether the binding sites for 8-azatropanes are the same as those for other 8-heterotropanes. A comparison of these compounds with their progenitor tropanes cast into doubt the existence of proximal binding sites on the DAT, and offered support for the existence of different binding sites for the 8-azatropanes compared with 8-oxa- and 8-thiatropanes. Indeed, 8-aza bivalent tropanes inhibited DAT with potency about 10-fold lower (DAT: IC50 = 31 nM) than their monovalent counterparts. Furthermore, bivalent ligands in which one or both of the tropanes was devoid of an amine suffered a further loss of inhibitory potency. We conclude that it is unlikely that there exist two tropane binding sites in close proximity to one another on either the DAT or SERT. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.009
• 作为产物：
  描述：

  丁二酸酐 、 (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-hydroxymethyl-8-oxabicyclo[3.2.1]octane 在 二甲基十二/十四烷基叔胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以100%的产率得到(1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(3-carboxypropionyloxymethyl)-8-oxabicyclo[3.2.1]octane
  参考文献：
  名称：

  The synthesis of bivalent 2β-carbomethoxy-3β-(3,4-dichlorophenyl)-8-heterobicyclo[3.2.1]octanes as probes for proximal binding sites on the dopamine and serotonin transporters

  摘要：

  3-Aryltropanes have been widely explored for potential medications for remediation of cocaine abuse. Research has focused predominantly on 8-azatropanes and it is now well recognized that these compounds can be designed to manifest varied selectivity and potency for inhibition of the dopamine, serotonin, and norepinephrine uptake systems. We had reported that the 8-nitrogen atom present in the 3-aryltropanes is not essential for tropanes to bind to monoamine uptake systems. We demonstrated that compounds in which the amine had been exchanged for an ether or a thioether retained binding potency and selectivity. We have now designed bivalent compounds in which two tropane moieties are linked by an intervening chain. These 8-homo- and 8-heterotropane bivalent compounds allowed a search for adjacent tropane binding sites on the DAT as well as a further exploration of whether the binding sites for 8-azatropanes are the same as those for other 8-heterotropanes. A comparison of these compounds with their progenitor tropanes cast into doubt the existence of proximal binding sites on the DAT, and offered support for the existence of different binding sites for the 8-azatropanes compared with 8-oxa- and 8-thiatropanes. Indeed, 8-aza bivalent tropanes inhibited DAT with potency about 10-fold lower (DAT: IC50 = 31 nM) than their monovalent counterparts. Furthermore, bivalent ligands in which one or both of the tropanes was devoid of an amine suffered a further loss of inhibitory potency. We conclude that it is unlikely that there exist two tropane binding sites in close proximity to one another on either the DAT or SERT. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.009