(6-氟吡啶-3-基)-三甲基锡烷 | 660847-68-7

• 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
• 中文名称: (6-氟吡啶-3-基)-三甲基锡烷
• 英文名称: 2-fluoro-5-trimethylstannylpyridine
• 英文别名: 2-fluoro-5-trimethyltinpyridine；2-fluoro-5-trimethylstannanyl-pyridine；2-Fluoro-5-(trimethylstannyl)pyridine；(6-fluoropyridin-3-yl)-trimethylstannane
• CAS: 660847-68-7
• 化学式: C₈H₁₂FNSn
• 分子量: 259.898
• InChiKey: AALHELSFJBDUBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.77
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (6-氟吡啶-3-基)-三甲基锡烷 在 四(三苯基膦)钯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 2-Chloro-6'-fluoro-5-((S)-1-pyrrolidin-2-ylmethoxy)-[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

文献信息

• WO2008/138834
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of a [2-Pyridinyl-18F]-labelled fluoro derivative of (−)-Cytisine as a candidate radioligand for brain nicotinic α4β2 receptor imaging with PET
  作者：Gaëlle Roger、Béatrice Lagnel、Jacques Rouden、Laurent Besret、Héric Valette、Stéphane Demphel、JaganMohan Gopisetti、Christine Coulon、Michele Ottaviani、Lori A Wrenn、Sharon R Letchworth、Georg A Bohme、Jesus Benavides、Marie-Claire Lasne、Michel Bottlaender、Frédéric Dollé

  DOI：10.1016/j.bmc.2003.09.042

  日期：2003.12

  In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K-i values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T-1/2: 119.8 min) using an efficient two-step radiochemical process [(a) nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b) TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3, 2-3 C-i/mumol or 74-111 GBq/pmol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [F-18]fluoride production batch (20-45% non decay-corrected yield based on the starting [F-18]fluoride). The in vivo pharmacological profile of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[H-3]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) does not have the required properties for imaging nAChRs using PET. (C) 2003 Elsevier Ltd. All rights reserved.
• 5-Substituted Derivatives of 6-Halogeno-3-((2-(<i>S</i>)-azetidinyl)methoxy)pyridine and 6-Halogeno-3-((2-(<i>S</i>)-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
  作者：Yi Zhang、Olga A. Pavlova、Svetlana I. Chefer、Andrew W. Hall、Varughese Kurian、LaVerne L. Brown、Alane S. Kimes、Alexey G. Mukhin、Andrew G. Horti

  DOI：10.1021/jm030432v

  日期：2004.5.1

  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.