(S)-5-tributylstannyl-nicotine | 188399-51-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (S)-5-tributylstannyl-nicotine
• CAS: 188399-51-1
• 化学式: C₂₂H₄₀N₂Sn
• 分子量: 451.283
• InChiKey: ADKDMUGQORLESY-CZEDPBFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.73
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  4.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-5-tributylstannyl-nicotine 在 一氯化碘 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以40%的产率得到(S)-3-iodo-5-(1-methylpyrrolidin-2-yl)pyridine
  参考文献：
  名称：

  Synthesis and Characterization of Radioiodinated (S)-5-Iodonicotine: A New Ligand for Potential Imaging of Brain Nicotinic Cholinergic Receptors by Single Photon Emission Computed Tomography.

  摘要：

  (S)-5-Iodonicotine (4a)是一种(S)-尼古丁类似物，在吡啶环的5-位被碘化，该化合物被合成并评估为一种潜在的放射性药物，可用于通过单光子发射计算机断层扫描（SPECT）研究大脑尼古丁受体。[125I]-(S)-5-碘烟碱（[125I]-4a）是在不添加载体的条件下通过碘锡烷化反应合成的，并通过高效液相色谱法（HPLC）纯化。根据[3H]胞嘧啶从大鼠大脑皮层膜结合位点移位的情况，测定了 4a 与大脑尼古丁受体的结合亲和力。结合数据显示，4a 的亲和力与（S）-尼古丁的亲和力相同，比（R）-对映体（4b）的亲和力高 80 倍。对小鼠的生物分布研究表明，[<125;>I]-4a 在大脑中的吸收迅速而深刻。通过自显影法对大鼠进行的区域脑分布研究表明，[125I]-4a 在丘脑中密集聚集，在大脑皮层和纹状体中处于中间位置，而在小脑中则不太明显。此外，施用（S）-尼古丁会减少丘脑对[125I]-4a的吸收，并导致小脑中的放射性水平几乎相同。与(S)-对映体（[125I]-4a）相比，[125I]-(R)-5-碘烟碱（[125I]-4b）在大脑中的洗脱速度更快，在大脑中的区域分布范围更小。因此，4a与体内脑尼古丁受体结合，碘123标记的4a可能是一种潜在的放射性配体，可用于SPECT体内脑尼古丁受体研究。

  DOI：

  10.1248/cpb.45.284

文献信息

• Application of (125I)(S)-5-Iodonicotine, a New Radioiodinated Ligand, in the Assay of Nicotinic Acetylcholine Receptor Binding in the Brain.
  作者：Hideo SAJI、Akira WATANABE、Yasushi KIYONO、Yasuhiro MAGATA、Yasuhiko IIDA、Yuuki TAKAISHI、Akira YOKOYAMA

  DOI：10.1248/bpb.18.1463

  日期：——

  [125I] (S)-5-Iodonicotine was prepared and its application in the assay of nicotinic acetylcholine receptor binding in the brain was studied. [125I] (S)-5-Iodonicotine bound to the rat cortical membrane with high affinity (Kd, 15.0nM). Various nicotinic cholinergic compounds showed competition with [125I] (S)-5-iodonicotine for the binding sites in the rat cortical membrane, and the specificity of its binding was correlated well with that of [3H] cytisine (r=0.98). These findings suggest that [125I] (S)-5-iodonicotine binds to the same sites as [3H] cytisine and indicate that [125I] (S)-5-iodonicotine can be applied as a brain nicotine receptor binding assay.
• Synthesis and Characterization of Radioiodinated (S)-5-Iodonicotine: A New Ligand for Potential Imaging of Brain Nicotinic Cholinergic Receptors by Single Photon Emission Computed Tomography.
  作者：Hideo SAJI、Akira WATANABE、Yasuhiro MAGATA、Yoshiro OHMOMO、Yasushi KIYONO、Yoshihisa YAMADA、Yasuhiko IIDA、Yoshiharu YONEKURA、Junji KONISHI、Akira YOKOYAMA

  DOI：10.1248/cpb.45.284

  日期：——

  (S)-5-Iodonicotine (4a), an (S)-nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by single photon emission computerized tomography (SPECT). [125I]-(S)-5-Iodonicotine ([125I]-4a) was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC). The binding affinity of 4a for brain nicotine receptors was measured in terms of displacement of [3H]cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of 4a was the same as that of (S)-nicotine and 80-fold higher than that of the (R)-enantiomer (4b). Biodistribution studies in mice disclosed that the brain uptake of [<125;>I]-4a was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125I]-4a was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. Furthermore, the administration of (S)-nicotine reduced the uptake of [125I]-4a in the thalamus and resulted in a nearly identifal level of radioactivity in the cerebellum. [125I]-(R)-5-Iodonicotine ([125I]-4b) showed more rapid washout from the brain and a less extensive regional cerebral distribution than the (S)-enantiomer ([125I]-4a). Thus, 4a bound to brain nicotine receptors in vivo, and therefore iodine-123-labeled 4a may be a potential radioligand for use in in vivo cerebral nicotinic receptor studies by SPECT.

  (S)-5-Iodonicotine (4a)是一种(S)-尼古丁类似物，在吡啶环的5-位被碘化，该化合物被合成并评估为一种潜在的放射性药物，可用于通过单光子发射计算机断层扫描（SPECT）研究大脑尼古丁受体。[125I]-(S)-5-碘烟碱（[125I]-4a）是在不添加载体的条件下通过碘锡烷化反应合成的，并通过高效液相色谱法（HPLC）纯化。根据[3H]胞嘧啶从大鼠大脑皮层膜结合位点移位的情况，测定了 4a 与大脑尼古丁受体的结合亲和力。结合数据显示，4a 的亲和力与（S）-尼古丁的亲和力相同，比（R）-对映体（4b）的亲和力高 80 倍。对小鼠的生物分布研究表明，[<125;>I]-4a 在大脑中的吸收迅速而深刻。通过自显影法对大鼠进行的区域脑分布研究表明，[125I]-4a 在丘脑中密集聚集，在大脑皮层和纹状体中处于中间位置，而在小脑中则不太明显。此外，施用（S）-尼古丁会减少丘脑对[125I]-4a的吸收，并导致小脑中的放射性水平几乎相同。与(S)-对映体（[125I]-4a）相比，[125I]-(R)-5-碘烟碱（[125I]-4b）在大脑中的洗脱速度更快，在大脑中的区域分布范围更小。因此，4a与体内脑尼古丁受体结合，碘123标记的4a可能是一种潜在的放射性配体，可用于SPECT体内脑尼古丁受体研究。