1-azabicyclo<2.2.2>oct-3-yl α-hydroxy-α-phenyl-α-(1-propyn-3-yl)acetate | 82326-71-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 1-azabicyclo<2.2.2>oct-3-yl α-hydroxy-α-phenyl-α-(1-propyn-3-yl)acetate
• 英文别名: 3-quinuclidinyl α-hydroxy-α-2-propargylphenylacetate；1-Azabicyclo[2.2.2]octan-3-yl 2-hydroxy-2-phenylpent-4-ynoate
• CAS: 82326-71-4
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: DXMZBTUMAXQARJ-UHFFFAOYSA-N

物化性质

• 沸点：
  454.0±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-azabicyclo<2.2.2>oct-3-yl α-hydroxy-α-phenyl-α-(1-propyn-3-yl)acetate 在 偶氮二异丁腈 、 碘 、 三正丁基氢锡 作用下， 生成 1-azabicyclo<2.2.2>oct-3-yl α-hydroxy-α-(1-iodo-1-propen-3-yl)-α-phenylacetate
  参考文献：
  名称：

  Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl .alpha.-hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography

  摘要：

  1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP, 3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity [125]IQNP ([I-125]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide. In in vitro receptor binding studies, 3 demonstrated high affinity for M1 (K(i) = 0.78 nM), M2 (K(i) = 1.06 nM), and M3 (K(i) = 0.27 nM) subtypes. In vivo biodistribution studies in female rats [I-125]-3 demonstrated high uptake in areas rich in muscarinic receptors such as the brain (cortex and striatum) and the heart. Blocking studies were performed with a series of receptor specific agents and demonstrated that the uptake of [I-125]-3 was selective and specific for cerebral muscarinic receptor rich areas and that the binding to m-AChR is reversible. The high-yield preparation and specificity and selectivity of high specific activity [I-125]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT).

  DOI：

  10.1021/jm00059a009
• 作为产物：
  描述：

  苯甲酰甲酸乙酯 在 sodium 、 锌 作用下， 以 甲苯 为溶剂， 反应 29.5h， 生成 1-azabicyclo<2.2.2>oct-3-yl α-hydroxy-α-phenyl-α-(1-propyn-3-yl)acetate
  参考文献：
  名称：

  Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl .alpha.-hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography

  摘要：

  1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP, 3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity [125]IQNP ([I-125]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide. In in vitro receptor binding studies, 3 demonstrated high affinity for M1 (K(i) = 0.78 nM), M2 (K(i) = 1.06 nM), and M3 (K(i) = 0.27 nM) subtypes. In vivo biodistribution studies in female rats [I-125]-3 demonstrated high uptake in areas rich in muscarinic receptors such as the brain (cortex and striatum) and the heart. Blocking studies were performed with a series of receptor specific agents and demonstrated that the uptake of [I-125]-3 was selective and specific for cerebral muscarinic receptor rich areas and that the binding to m-AChR is reversible. The high-yield preparation and specificity and selectivity of high specific activity [I-125]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT).

  DOI：

  10.1021/jm00059a009

文献信息

• Analogs of 3-quinuclidinyl benzilate
  作者：W. J. Rzeszotarski、R. E. Gibson、W. C. Eckelman、D. A. Simms、E. M. Jagoda、N. L. Ferreira、R. C. Reba

  DOI：10.1021/jm00351a020

  日期：1982.9

  dog ventricular muscle measured. We have determined that the muscarinic receptor can to a different degree accommodate either a halogen in the ortho, meta, or para position of one phenyl ring or the replacement of one phenyl ring with an alkyl group. Our in vitro competition studies show that the affinities lie within a 270-fold range, from the highest affinity compound, 3-quinuclidinyl alpha-hydro

  已经合成了许多3-奎宁环烷基苯磺酸盐（QNB）的类似物，并测量了它们与来自大鼠或狗心室肌的毒蕈碱受体的亲和力。我们已经确定毒蕈碱受体可以在不同程度上容纳一个苯环的邻位，间位或对位中的卤素或一个烷基取代一个苯环。我们的体外竞争研究表明，亲和力处于270倍范围内，从亲和力最高的化合物3-奎宁环烯基α-羟基-α-环戊基苯基乙酸酯（2）到亲和力最低的化合物3-奎宁环烷基α-羟基- α-2-炔丙基苯基乙酸酯（11）。
• Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl .alpha.-hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography
  作者：D. W. McPherson、D. L. DeHaven-Hudkins、A. P. Callahan、F. F. Knapp

  DOI：10.1021/jm00059a009

  日期：1993.4

  1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP, 3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity [125]IQNP ([I-125]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide. In in vitro receptor binding studies, 3 demonstrated high affinity for M1 (K(i) = 0.78 nM), M2 (K(i) = 1.06 nM), and M3 (K(i) = 0.27 nM) subtypes. In vivo biodistribution studies in female rats [I-125]-3 demonstrated high uptake in areas rich in muscarinic receptors such as the brain (cortex and striatum) and the heart. Blocking studies were performed with a series of receptor specific agents and demonstrated that the uptake of [I-125]-3 was selective and specific for cerebral muscarinic receptor rich areas and that the binding to m-AChR is reversible. The high-yield preparation and specificity and selectivity of high specific activity [I-125]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT).