2-(8-methyl-8-azabicyclo[3.2.1]oct-3-ylidene)ethanol | 380601-96-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 2-(8-methyl-8-azabicyclo[3.2.1]oct-3-ylidene)ethanol
• 英文别名: 2-(8-Methyl-8-azabicyclo[3.2.1]octan-3-ylidene)ethanol
• CAS: 380601-96-7
• 化学式: C₁₀H₁₇NO
• 分子量: 167.251
• InChiKey: JSWVKBZMDMJAQN-UHFFFAOYSA-N

物化性质

• 沸点：
  277.4±20.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(8-methyl-8-azabicyclo[3.2.1]oct-3-ylidene)ethanol 、 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 3-[2-[Bis(4-fluorophenyl)methoxy]ethylidene]-8-methyl-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Tropane-like 1-{2-[Bis(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR 12909) Analogues

  摘要：

  We have prepared azabicyclo [3.2.1] derivatives (C-3-substituted tropanes) that bind with high affinity to the dopamine transporter and inhibit dopamine reuptake. Within the series, 3-{2-[bis-(4-fluorophenyl)methoxyl ethylidene}-8-methyl-8-azabicyclo [3.2.1] octane (8) was found to have the highest affinity and selectivity for the dopamine transporter. These azabicyclo [3.2.1] (bridged piperidine) series of compounds differ from the well-known benztropines by a 2-carbon spacer between C-3 and a diarylmethoxy moiety. Interestingly, these new compounds demonstrated a much lower affinity for the muscarinic-1 site, at least a 100-fold decrease compared to benztropine. Replacing N-methyl with N-phenylpropyl in two of the compounds resulted in a 3-10-fold increase in binding affinity for the dopamine transporter. However, those compounds lost selectivity for the dopamine transporter over the serotonin transporter. Replacement of the ether oxygen in the diarylmethoxy moiety with a nitrogen atom gave relatively inactive amines, indicating the important role which is played by the ether oxygen in transporter binding. Reduction of the C-3 double bond in 8 gave 3 alpha -substituted tropanes, as shown by X-ray crystallographic analyses of 11, 12, and 19. The 3 alpha -substituted tropanes had lower affinity and less selectivity than the comparable unsaturated ligands.

  DOI：

  10.1021/jm0101592
• 作为产物：
  描述：

  ethyl (8-methyl-8-azabicyclo<3.2.1>oct-3-ylidene)acetate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以100%的产率得到2-(8-methyl-8-azabicyclo[3.2.1]oct-3-ylidene)ethanol
  参考文献：
  名称：

  Design and Synthesis of Potent Antileishmanial Cycloalkylidene-Substituted Ether Phospholipid Derivatives

  摘要：

  Two series of novel ether phospholipids (EPs) have been synthesized. The first includes cyclodecylideneor cyclopentadecylidene-substituted EPs carrying N,N,N-trimethylammonium or N-methylpiperidino or N-methylmorpholino head groups. The second series encompasses more rigid head groups in combination with cycloalkylidene moieties in the lipid portion. In addition, hydrogenated derivatives were obtained. All the new analogues, except 33, were 1.5- to 62-fold more potent than miltefosine against the intracellular L. infantum, and the most active ones were also less cytotoxic against the human monocytic cell line THP1 and less hemolytic than miltefosine. The analogues that combine high potency with low cytotoxicity and hemolytic activity were 19, 37, 2123, 38, 39, and 40. Cyclopentadecylpentylphosphocholine (38) possesses an IC50 of 0.7 mu M against L. infantum amastigotes and is the least cytotoxic analogue, since it does not present toxicity against THP1 macrophages, even at a concentration that is 800-fold the antiparasitic IC50 value, and does not present significant hemolytic activity.

  DOI：

  10.1021/jm701166b