2-bromo-3-iodo-5-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)pyridine | 697300-71-3

• 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: 2-bromo-3-iodo-5-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)pyridine
• 英文别名: 1,1-Dimethylethyl (2S)-2-[[(6-bromo-5-iodo-3-pyridinyl)oxy]methyl]-1-azetidinecarboxylate；tert-butyl (2S)-2-[(6-bromo-5-iodopyridin-3-yl)oxymethyl]azetidine-1-carboxylate
• CAS: 697300-71-3
• 化学式: C₁₄H₁₈BrIN₂O₃
• 分子量: 469.117
• InChiKey: SXPCUICDNCEHFJ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.66
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-bromo-3-iodo-5-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)pyridine 在 copper(l) iodide 、 四(三苯基膦)钯 、 potassium iodide 作用下， 以 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 1.83h， 生成 5-((S)-1-Azetidin-2-ylmethoxy)-2-iodo-[3,3']bipyridinyl; compound with trifluoro-acetic acid
  参考文献：
  名称：

  5-Substituted Derivatives of 6-Halogeno-3-((2-(S)-azetidinyl)methoxy)pyridine and 6-Halogeno-3-((2-(S)-pyrrolidinyl)methoxy)pyridine with Low Picomolar Affinity for α4β2 Nicotinic Acetylcholine Receptor and Wide Range of Lipophilicity:  Potential Probes for Imaging with Positron Emission Tomography

  摘要：

  Potential positron emission tomography (PET) ligands with low picomolar affinity at the nicotinic acetylcholine receptor (nAChR) and with lipophilicity (log D) ranging from -1.6 to +1.5 have been synthesized. Most members of the series, which are derivatives of 5-substituted-6-halogeno-A-85380, exhibited a higher binding affinity at alpha4beta2-nAChRs than epibatidine. An analysis, by molecular modeling, revealed an important role of the orientation of the additional heterocyclic ring on the binding affinity of the ligands with nAChRs. The existing nicotinic pharmacophore models do not accommodate this finding. Two compounds of the series, 6-[F-18]-fluoro-5-(pyridin-3-yl)-A-85380 ([F-18]31) and 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2- [F-18]-fluoropyridin-5-yl)pyridine) ([F-18]35), were radiolabeled with F-18. Comparison of PET data for [F-18]31 and 2-[F-18]FA shows the influence of lipophilicity on the binding potential. Our recent PET studies with [F-18]35 demonstrated that its binding potential values in Rhesus monkey brain were ca. 2.5 times those of 2-[F-18]FA. Therefore, [F-18]35 and several other members of the series, when radiolabeled, will be suitable for quantitative imaging of extrathalamic nAChRs.

  DOI：

  10.1021/jm030432v
• 作为产物：
  描述：

  3-碘-2-羟基-5-硝基吡啶 在 氢氧化钾 、 tetrafluoroboric acid 、 铁粉 、 溶剂黄146 、 三苯基膦 、 sodium nitrite 、 偶氮二甲酸二乙酯 、 三溴氧磷 作用下， 以 四氢呋喃 、 喹啉 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 21.33h， 生成 2-bromo-3-iodo-5-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)pyridine
  参考文献：
  名称：

  5-Substituted Derivatives of 6-Halogeno-3-((2-(S)-azetidinyl)methoxy)pyridine and 6-Halogeno-3-((2-(S)-pyrrolidinyl)methoxy)pyridine with Low Picomolar Affinity for α4β2 Nicotinic Acetylcholine Receptor and Wide Range of Lipophilicity:  Potential Probes for Imaging with Positron Emission Tomography

  摘要：

  Potential positron emission tomography (PET) ligands with low picomolar affinity at the nicotinic acetylcholine receptor (nAChR) and with lipophilicity (log D) ranging from -1.6 to +1.5 have been synthesized. Most members of the series, which are derivatives of 5-substituted-6-halogeno-A-85380, exhibited a higher binding affinity at alpha4beta2-nAChRs than epibatidine. An analysis, by molecular modeling, revealed an important role of the orientation of the additional heterocyclic ring on the binding affinity of the ligands with nAChRs. The existing nicotinic pharmacophore models do not accommodate this finding. Two compounds of the series, 6-[F-18]-fluoro-5-(pyridin-3-yl)-A-85380 ([F-18]31) and 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2- [F-18]-fluoropyridin-5-yl)pyridine) ([F-18]35), were radiolabeled with F-18. Comparison of PET data for [F-18]31 and 2-[F-18]FA shows the influence of lipophilicity on the binding potential. Our recent PET studies with [F-18]35 demonstrated that its binding potential values in Rhesus monkey brain were ca. 2.5 times those of 2-[F-18]FA. Therefore, [F-18]35 and several other members of the series, when radiolabeled, will be suitable for quantitative imaging of extrathalamic nAChRs.

  DOI：

  10.1021/jm030432v