8-methyl-3-methylene-8-azabicyclo[3.2.1]octane

• 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: 8-methyl-3-methylene-8-azabicyclo[3.2.1]octane
• 英文别名: (1S,5R)-8-methyl-3-methylidene-8-azabicyclo[3.2.1]octane
• 化学式: C₉H₁₅N
• 分子量: 137.225
• InChiKey: VTTHRNBDRMKNKB-DTORHVGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  8-methyl-3-methylene-8-azabicyclo[3.2.1]octane 在 sodium tetrahydroborate 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 51.0h， 生成 [(1'S,5'R)-8',8'-dimethylspiro[4H-1,2-oxazole-5,3'-8-azoniabicyclo[3.2.1]octane]-3-yl]methanol;iodide
  参考文献：
  名称：

  A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake

  摘要：

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.004
• 作为产物：
  描述：

  tropinone 、 甲基三苯基溴化膦 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 8-methyl-3-methylene-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake

  摘要：

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.004

文献信息

• Design of α7 nicotinic acetylcholine receptor ligands in quinuclidine, tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in vitro and in rats evaluations of a [18F] quinuclidine derivative
  作者：Frédéric Pin、Johnny Vercouillie、Aziz Ouach、Sylvie Mavel、Zuhal Gulhan、Gabrielle Chicheri、Christian Jarry、Stephane Massip、Jean-Bernard Deloye、Denis Guilloteau、Franck Suzenet、Sylvie Chalon、Sylvain Routier

  DOI：10.1016/j.ejmech.2014.04.057

  日期：2014.7

  In this report, we describe the synthesis of a novel library of alpha 7 nAChR ligands based on the modulation of the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly synthesized under stereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor with Ki measured between 14 and 133 nM. The best fluorinated candidate was selected and radiolabeled. The potent [F-18]4 PET tracer was evaluated in rats and its brain accumulation quantified. (C) 2014 Elsevier Masson SAS. All rights reserved.
• A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake
  作者：Clelia Dallanoce、Mara Canovi、Carlo Matera、Tiziana Mennini、Marco De Amici、Marco Gobbi、Carlo De Micheli

  DOI：10.1016/j.bmc.2012.09.004

  日期：2012.11

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.