2-fluoro-4-trimethyltinpyridine | 697300-76-8

• 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-fluoro-4-trimethyltinpyridine
• 英文别名: 2-Fluoro-4-(trimethylstannyl)pyridine；(2-fluoropyridin-4-yl)-trimethylstannane
• CAS: 697300-76-8
• 化学式: C₈H₁₂FNSn
• 分子量: 259.898
• InChiKey: WHGNMLZMLDOAFM-UHFFFAOYSA-N

物化性质

• 沸点：
  234.7±50.0 °C(Predicted)

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：

  2-fluoro-4-trimethyltinpyridine 在 四(三苯基膦)钯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 5-((S)-1-Azetidin-2-ylmethoxy)-2-chloro-2'-fluoro-[3,4']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

• Derivatives of (−)-7-Methyl-2-(5-(pyridinyl)pyridin-3-yl)-7-azabicyclo[2.2.1]heptane Are Potential Ligands for Positron Emission Tomography Imaging of Extrathalamic Nicotinic Acetylcholine Receptors
  作者：Yongjun Gao、Andrew G. Horti、Hiroto Kuwabara、Hayden T. Ravert、John Hilton、Daniel P. Holt、Anil Kumar、Mohab Alexander、Christopher J. Endres、Dean F. Wong、Robert F. Dannals

  DOI：10.1021/jm070224t

  日期：2007.8.1

  and 18F as potential radioligands for positron emission tomography imaging of the nAChR. In vivo enantioselectivity of the radiolabeled (-)-7-methyl-2-(5-(pyridinyl)pyridin-3-yl)-7-azabicyclo[2.2.1]heptane derivatives was observed in biodistribution studies in rodents and baboon. One of the radiolabeled compounds, (-)-7-methyl-2-exo-[3'-(2-[18F]fluoropyridin-5-yl))-5'-pyridinyl]-7-azabicyclo[2. 2.1]heptane

  合成了一系列新型的外消旋7-甲基-2-（5-（吡啶基）吡啶-3-基）-7-氮杂双环[2.2.1]庚烷衍生物，其在烟碱乙酰胆碱受体（nAChRs）上具有皮摩尔的体外结合亲和力，并它们的对映体通过半制备手性HPLC拆分。（-）-对映异构体显示出比相应的（+）-对映异构体显着更大的体外抑制结合亲和力。具有最佳结合亲和力的化合物已用正电子发射同位素11C和18F进行了放射性标记，作为nAChR的正电子发射断层成像的潜在放射性配体。在啮齿动物和狒狒的生物分布研究中观察到放射性标记的（-）-7-甲基-2-（5-（吡啶基）吡啶3-3-基）-7-氮杂双环[2.2.1]庚烷衍生物的体内对映选择性。放射性标记的化合物之一，（-）-7-甲基-2-exo- [3' -（2- [18F]氟吡啶-5-基）-5'-吡啶基] -7-氮杂双环[2。2.1]庚烷作为狒狒脑中丘脑外nAChR成像的首个实用PET放射性配体表现出良好的性能，并有望进一步用于人体研究。
• Discovery of (−)-7-Methyl-2-<i>exo</i>-[3′-(6-[¹⁸F]fluoropyridin-2-yl)-5′-pyridinyl]-7-azabicyclo[2.2.1]heptane, a Radiolabeled Antagonist for Cerebral Nicotinic Acetylcholine Receptor (α4β2-nAChR) with Optimal Positron Emission Tomography Imaging Properties
  作者：Yongjun Gao、Hiroto Kuwabara、Charles E. Spivak、Yingxian Xiao、Kenneth Kellar、Hayden T. Ravert、Anil Kumar、Mohab Alexander、John Hilton、Dean F. Wong、Robert F. Dannals、Andrew G. Horti

  DOI：10.1021/jm800323d

  日期：2008.8.1

  Several isomers of 7-methyl-2-exo-([F-18]fluoropyridinyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane have been developed as radioligands with optimized brain kinetics for PET imaging of nAChR. The binding assay demonstrated that all isomers are beta-nAChR selective ligands with K-i = 0.02-0.3 nM. The experimental lipophilicity values of all isomers were in the. optimal range for the cerebral radioligands (log D-7.4=0.67-0.99). The isomers with higher binding affinity manifested slow baboon brain kinetics, whereas the isomer with the lowest binding affinity (K-i=0.3 nM) ((-)-7-methyl-2-exo-[3'-(6-[F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, [F-18](-)-6c) and greatest lipophilicity (log D-7.4=0.99) exhibited optimal brain kinetics. [F-18](-)-6c manifests a unique combination of the optimally rapid brain kinetics, high BP and brain uptake, and favorable metabolic profile. Pharmacological studies showed that (-)-6c is an alpha 4 beta 2-nAChR antagonist with low side effects in mice. This combination of imaging properties suggests that [F-18]-(-)-6c is a potentially superior replacement for 2-[F-18]fluoro-A-85380 and 6-[F-18]fluoro-A-85380, the only available nAChR PET radioligands for humans.