2-bromo-4-trimethyltinpyridine | 697300-77-9

• 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-4-trimethyltinpyridine
• 英文别名: 2-bromo-4-(trimethylstannyl)pyridine；2-Bromo-4-(trimethylstannyl)-pyridine；(2-bromopyridin-4-yl)-trimethylstannane
• CAS: 697300-77-9
• 化学式: C₈H₁₂BrNSn
• 分子量: 320.804
• InChiKey: XXKTZXMVLJIZAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 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：
  1

反应信息

• 作为反应物：
  描述：

  2-bromo-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'-bromo-2-chloro-[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

• 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.
• 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.