2,6-bis(hex-1-ynyl)pyridine | 500228-78-4

• 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: 2,6-bis(hex-1-ynyl)pyridine
• 英文别名: 2,6-di(hex-1-ynyl)pyridine；2,6-di-1-hexynylpyridine；Fotcfqzwhavric-uhfffaoysa-
• CAS: 500228-78-4
• 化学式: C₁₇H₂₁N
• 分子量: 239.36
• InChiKey: FOTCFQZWHAVRIC-UHFFFAOYSA-N

物化性质

• 沸点：
  383.0±27.0 °C(Predicted)
• 密度：
  0.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  2,6-bis(hex-1-ynyl)pyridine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 2,6-dihexyl-1-methylpyridinium trifluoromethanesulfonate
  参考文献：
  名称：

  Structure–Affinity Relationships (SARs) and Structure–Kinetics Relationships (SKRs) of K_v11.1 Blockers

  摘要：

  K(v)11.1 (hERG) blockers with comparable potencies but different binding kinetics might display divergent proarrhythmic risks. In the present study, we explored structure-kinetics relationships in four series of K(v)11.1 blockers next to their structure affinity relationships. We learned that despite dramatic differences in affinities and association rates, there were hardly any variations in the dissociation rate constants of these molecules with residence times (RTs) of a few minutes only. Hence, we synthesized 16 novel molecules, in particular in the pyridinium class of compounds, to further address this peculiar phenomenon. We found molecules with very short RTs (e.g., 0.34 min for 37) and much longer RTs (e.g., 105 min for 38). This enabled us to construct a k(on)-k(off)-K-D kinetic map for all compounds and subsequently divide the map into four provisional quadrants, providing a possible framework for a further and more precise categorization of K(v)11.1 blockers. Additionally, two representative compounds (21 and 38) were tested in patch clamp assays, and their RTs were linked to their functional IC50 values. Our findings strongly suggest the importance of the simultaneous study of ligand affinities and kinetic parameters, which may help to explain and predict K(v)11.1-mediated cardiotoxicity.

  DOI：

  10.1021/acs.jmedchem.5b00518
• 作为产物：
  描述：

  2,6-二溴吡啶 、 1-己炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 2,6-bis(hex-1-ynyl)pyridine
  参考文献：
  名称：

  走向可以沿着轨道定向行走的金属配合物：用钯 (II) 脚控制分子双足动物的步进

  摘要：

  我们报告了双金属分子双足动物在三足轨道上的设计、合成和操作。“助行器”具有钯 (II) 复合“脚”，可以通过可逆质子化选择性地在轨道上的 4-二甲氨基吡啶和吡啶配体位点之间移动，而助行器通过动力学惰性的铂始终保持附着在轨道上（ II) 复足。三个配体结合位点的取代模式，连同金属-配体配位键的动力学稳定性，为两个位置异构体提供了高度的亚稳定性，这意味着改变轨道的化学状态不会自动引发步入没有额外的刺激（在配位溶剂存在下加热）。

  DOI：

  10.1021/ja4123973

文献信息

• Toward Metal Complexes That Can Directionally Walk Along Tracks: Controlled Stepping of a Molecular Biped with a Palladium(II) Foot
  作者：Jonathon E. Beves、Victor Blanco、Barry A. Blight、Romen Carrillo、Daniel M. D’Souza、David Howgego、David A. Leigh、Alexandra M. Z. Slawin、Mark D. Symes

  DOI：10.1021/ja4123973

  日期：2014.2.5

  report on the design, synthesis, and operation of a bimetallic molecular biped on a three-foothold track. The "walker" features a palladium(II) complex "foot" that can be selectively stepped between 4-dimethylaminopyridine and pyridine ligand sites on the track via reversible protonation while the walker remains attached to the track throughout by means of a kinetically inert platinum(II) complex foot. The

  我们报告了双金属分子双足动物在三足轨道上的设计、合成和操作。“助行器”具有钯 (II) 复合“脚”，可以通过可逆质子化选择性地在轨道上的 4-二甲氨基吡啶和吡啶配体位点之间移动，而助行器通过动力学惰性的铂始终保持附着在轨道上（ II) 复足。三个配体结合位点的取代模式，连同金属-配体配位键的动力学稳定性，为两个位置异构体提供了高度的亚稳定性，这意味着改变轨道的化学状态不会自动引发步入没有额外的刺激（在配位溶剂存在下加热）。
• Rhodium-Catalyzed Addition of Arylboronic Acids to Alkynyl Aza-Heteroaromatic Compounds in Water
  作者：Mark Lautens、Masahiro Yoshida

  DOI：10.1021/jo0205255

  日期：2003.2.1

  Alkynyl heteroaromatic compounds reacted with arylboronic acids to give addition products in the presence of a rhodium catalyst. The best results were obtained when a novel pyridine-substituted water-soluble phosphine ligand was used. The reactions proceed to give trisubstituted alkenes from various arylboronic acids and alkynyl heteroaromatic compounds with high regioselectivity. Only alkynes with

  炔基杂芳族化合物与芳基硼酸反应，在铑催化剂的存在下得到加成产物。当使用新型吡啶取代的水溶性膦配体时，可获得最佳结果。反应进行以高区域选择性从各种芳基硼酸和炔基杂芳族化合物得到三取代的烯烃。如对螯合控制的加料所预期的那样，只有氮原子在三键附近的炔烃才被转化为相应的烯烃。
• Synthesis, Characterization, and Fluorescence Behavior of Twisted and Planar B₂N₂-Quaterphenyl Analogues
  作者：Cory A. Jaska、Warren E. Piers、Robert McDonald、Masood Parvez

  DOI：10.1021/jo0706574

  日期：2007.7.1

  quaterphenyl analogues containing BN ring linkages has been synthesized using primarily difunctional Lewis acidic diborabiphenyl moieties as molecular cores. Crystal structure analyses indicated the presence of large twist angles between adjacent aromatic rings in 1 and 3, which were also observed to possess nonfluorescent behavior due to a lack of molecular rigidity and insufficient BN character in

  一系列含有BN环键的平面和扭曲的杂芳族四元苯基类似物已被合成，主要使用双官能的Lewis酸性Diborabiphenyl部分作为分子核心。晶体结构分析表明，在1和3中相邻的芳环之间存在较大的扭曲角，并且由于缺乏分子刚度和在激发态下的B N特性不足，还观察到它们具有非荧光特性。与此相反，在相邻的环（经由乙炔环异构安装）之间的一个或两个桥接亚乙基的引入被发现，得到平坦的菲或芘的部分，这导致弱荧光行为（Φ ˚F = 0.02-0.16）的Ñ-Bu且Ph衍生物5 - 12。发射颜色的范围从绿色（λem = 521 nm）到红色（λem = 630 nm），主要取决于构象（2,2'- vs 4,4'-），发色团共轭的程度（菲与vs） ），以及存在的环外取代基的类型（n -Bu对Ph）。在某些情况下，观察到两个菲或pyr部分之间的通信，其特征在于相对于单体菲或pyr物种的红移改变了发射带。2,2'-异
• 10a-Aza-10b-borapyrenes: Heterocyclic Analogues of Pyrene with Internalized BN Moieties
  作者：Michael J. D. Bosdet、Warren E. Piers、Ted S. Sorensen、Masood Parvez

  DOI：10.1002/anie.200700591

  日期：2007.6.25
• Structure–Affinity Relationships (SARs) and Structure–Kinetics Relationships (SKRs) of K_v11.1 Blockers
  作者：Zhiyi Yu、Jacobus P. D. van Veldhoven、Julien Louvel、Ingrid M. E. ’t Hart、Martin B. Rook、Marcel A. G. van der Heyden、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1021/acs.jmedchem.5b00518

  日期：2015.8.13

  K(v)11.1 (hERG) blockers with comparable potencies but different binding kinetics might display divergent proarrhythmic risks. In the present study, we explored structure-kinetics relationships in four series of K(v)11.1 blockers next to their structure affinity relationships. We learned that despite dramatic differences in affinities and association rates, there were hardly any variations in the dissociation rate constants of these molecules with residence times (RTs) of a few minutes only. Hence, we synthesized 16 novel molecules, in particular in the pyridinium class of compounds, to further address this peculiar phenomenon. We found molecules with very short RTs (e.g., 0.34 min for 37) and much longer RTs (e.g., 105 min for 38). This enabled us to construct a k(on)-k(off)-K-D kinetic map for all compounds and subsequently divide the map into four provisional quadrants, providing a possible framework for a further and more precise categorization of K(v)11.1 blockers. Additionally, two representative compounds (21 and 38) were tested in patch clamp assays, and their RTs were linked to their functional IC50 values. Our findings strongly suggest the importance of the simultaneous study of ligand affinities and kinetic parameters, which may help to explain and predict K(v)11.1-mediated cardiotoxicity.

表征谱图