3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-6-tert-butyloxycarbonyl-3,6-diazabicyclo[3.1.1]heptane | 937030-48-3

• 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: 3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-6-tert-butyloxycarbonyl-3,6-diazabicyclo[3.1.1]heptane
• CAS: 937030-48-3
• 化学式: C₂₅H₃₀F₂N₂O₃
• 分子量: 444.522
• InChiKey: NKKBZZYURUJBPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.76
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  42.01
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-6-tert-butyloxycarbonyl-3,6-diazabicyclo[3.1.1]heptane 在 甲酸 、 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 24.5h， 生成 (E)-1-(3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-3,6-diazabicyclo[3.1.1]heptan-6-yl)-3-(thiophen-2-yl)prop-2-en-1-one
  参考文献：
  名称：

  3-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}-6-substituted-3,6-diazabicyclo[3.1.1]heptanes as novel potent dopamine uptake inhibitors

  摘要：

  A series of analogues 2a-i related to 3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-8-(1H-indol-2-ylmethyl)-3,8-diazabicyclo[3.2. 1]octane (1) in which the 3,8-diazabicyclo[3.2. I]octane core was replaced by 3,6-diazabicyclo[3.1.1]heptane ring system has been synthesized and evaluated for their ability to inhibit DA reuptake into striatal nerve endings (synaptosomes). Biological data showed that compound 2a, the closest analogue of lead 1, possessed an increased reuptake inhibition activity over 1 (2a, K-i = 5.5 nM). Replacement of the indole ring with bioisosteric aromatic rings-benzothiophene (2b), benzofurane (2c), or indene (2d)-resulted, with the exception of 2d, in a double digit nanomolar activity. Changing the indenyl moiety of 2d with simplified aryl groups led to compounds 2e-h which displayed a similar or slightly decreased activity with respect to the ground term. Naphthalene derivative (2i) demonstrated a weaker activity than aromatic analogues. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.035
• 作为产物：
  描述：

  3,6-二氮杂双环[3.1.1]庚烷-6-羧酸叔丁酯 、 2-[bis(4-fluorophenyl)methoxy]ethyl iodide 在 potassium carbonate 作用下， 以 various solvent(s) 为溶剂， 反应 17.0h， 以67%的产率得到3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-6-tert-butyloxycarbonyl-3,6-diazabicyclo[3.1.1]heptane
  参考文献：
  名称：

  3-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}-6-substituted-3,6-diazabicyclo[3.1.1]heptanes as novel potent dopamine uptake inhibitors

  摘要：

  A series of analogues 2a-i related to 3-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-8-(1H-indol-2-ylmethyl)-3,8-diazabicyclo[3.2. 1]octane (1) in which the 3,8-diazabicyclo[3.2. I]octane core was replaced by 3,6-diazabicyclo[3.1.1]heptane ring system has been synthesized and evaluated for their ability to inhibit DA reuptake into striatal nerve endings (synaptosomes). Biological data showed that compound 2a, the closest analogue of lead 1, possessed an increased reuptake inhibition activity over 1 (2a, K-i = 5.5 nM). Replacement of the indole ring with bioisosteric aromatic rings-benzothiophene (2b), benzofurane (2c), or indene (2d)-resulted, with the exception of 2d, in a double digit nanomolar activity. Changing the indenyl moiety of 2d with simplified aryl groups led to compounds 2e-h which displayed a similar or slightly decreased activity with respect to the ground term. Naphthalene derivative (2i) demonstrated a weaker activity than aromatic analogues. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.035