2-chloro-5-((1-(tert-butoxycarbonyl)-2(S)-azetidinyl)methoxy)-3-(2-bromopyridin-4-yl)pyridine | 697301-26-1

• 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: 2-chloro-5-((1-(tert-butoxycarbonyl)-2(S)-azetidinyl)methoxy)-3-(2-bromopyridin-4-yl)pyridine
• CAS: 697301-26-1
• 化学式: C₁₉H₂₁BrClN₃O₃
• 分子量: 454.751
• InChiKey: QQYFBVCJJKNRLK-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  64.55
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-chloro-5-((1-(tert-butoxycarbonyl)-2(S)-azetidinyl)methoxy)-3-(2-bromopyridin-4-yl)pyridine 在 copper(l) iodide 、 potassium iodide 作用下， 以 二甲基亚砜 为溶剂， 反应 2.5h， 以60%的产率得到2-chloro-5-((1-(tert-butoxycarbonyl)-2(S)-azetidinyl)methoxy)-3-(2-iodopyridin-4-yl)pyridine
  参考文献：
  名称：

  Synthesis of 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[18F]fluoropyridin-4-yl)pyridine ([18F]NIDA 522131), a novel potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by PET

  摘要：

  6-氯-3-((2-(S)-氮杂环丁基)甲氧基)-5-(2-[18F]氟吡啶-4-基)吡啶（[18F]NIDA 522131）是一种潜在的放射性配体，可通过正电子发射断层扫描研究丘脑外烟碱型乙酰胆碱受体，它是通过6-氯-3-((1-(叔丁氧羰基)-2-(S)-氮杂环丁基)甲氧基)-5-(2-碘吡啶-4-基)乙烯基)吡啶的无载体添加亲核[18F]氟化，然后进行酸性脱保护合成的。放射性合成的总放射化学产率为4-8%（未校正衰变），比活度范围为167-335 GBq/µmol（4500-9000 mCi/µmol），放射化学纯度大于99%。还描述了通过相应的溴衍生物2制备[18F]NIDA522131的方法。版权所有 © 2004 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.883
• 作为产物：
  描述：

  2-chloro-3-iodo-5-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)pyridine 、 2-bromo-4-trimethyltinpyridine 在 四(三苯基膦)钯 作用下， 以 甲苯 为溶剂， 以44%的产率得到2-chloro-5-((1-(tert-butoxycarbonyl)-2(S)-azetidinyl)methoxy)-3-(2-bromopyridin-4-yl)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