2,6-bis(phenoxymethyl)pyridine | 66433-94-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,6-bis(phenoxymethyl)pyridine
• CAS: 66433-94-1
• 化学式: C₁₉H₁₇NO₂
• 分子量: 291.349
• InChiKey: GGMVMHVPZZUXBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-bis(phenoxymethyl)pyridine 、 三氟甲烷磺酸甲酯 以 二氯甲烷 为溶剂， 以43%的产率得到1-Methyl-2,6-bis(phenoxymethyl)pyridin-1-ium;trifluoromethanesulfonate
  参考文献：
  名称：

  Strategies To Reduce hERG K⁺Channel Blockade. Exploring Heteroaromaticity and Rigidity in Novel Pyridine Analogues of Dofetilide

  摘要：

  Drug-induced blockade of the human ether-a-go-go-related gene K+ channel (hERG) represents one of the major antitarget concerns in pharmaceutical industry. SAR studies of this ion channel have shed light on the structural requirements for hERG interaction but most importantly may reveal drug design principles to reduce hERG affinity. In the present study, a novel library of neutral and positively charged heteroaromatic derivatives of the class III antiarrhythmic agent dofetilide was synthesized and assessed for hERG affinity in radioligand binding and manual patch clamp assays. Structural modifications of the pyridine moiety, side chain, and peripheral aromatic moieties were evaluated, thereby revealing approaches for reducing hERG binding affinity. In particular, we found that the extra rigidity imposed close to the positively charged pyridine moiety can be very efficient in decreasing hERG affinity.

  DOI：

  10.1021/jm301564f
• 作为产物：
  描述：

  2,6-二氯甲基吡啶 、 苯酚 在 氢氧化钾 作用下， 生成 2,6-bis(phenoxymethyl)pyridine
  参考文献：
  名称：

  Kamalov, G. L.; Zakolodyazhnaya, O. V.; Manolova, A. V., Journal of general chemistry of the USSR, 1992, vol. 62, # 3.2, p. 561 - 566

  摘要：

  DOI：

文献信息

• Synthesis and characterization of new aromatic tweezers and complex formation with tropylium ion in 1,2-dichloroethane
  作者：Markku Lämsä、Sari Kiviniemi、Eeva-Riitta Kettukangas、Maija Nissinen、Jouni Pursiainen、Kari Rissanen

  DOI：10.1002/poc.392

  日期：2001.8

  spectroscopy were used to investigate the host–guest chemistry of the new ligands in complexation with tropylium tetrafluoroborate as a model aromatic cationic guest in 1,2-dichloroethane. The appearance of coloured charge-transfer absorption bands demonstrates the complex formation with a tropylium ion. The enlargement of aryl receptor size from phenyl and naphthyl to anthryl increases the stability of

  制备并表征了一系列带有苯基，萘基和蒽基受体单元的苯和吡啶镊子。1,3-双（9-甲醇蒽）甲基苯配体的X射线晶体结构（5）被报告。紫外可见光和NMR光谱用于研究与四氟硼酸对苯二酚在1，2-二氯乙烷中作为模型芳族阳离子客体络合的新配体的主体-客体化学性质。彩色电荷转移吸收带的出现表明与对离子形成了络合物。从苯基和萘基到蒽基的芳基受体大小的增加增加了复合物的稳定性。电子给体-受体相互作用是分子镊子络合的重要驱动力。对结果进行了讨论，并与先前研究的含有冠醚和豆荚的系统进行了比较。双蒽5和1,3-双（9-甲醇蒽）甲基吡啶（6）在通过电荷转移激发显示络合能力和分子内环加成方面特别有趣。版权所有©2001 John Wiley＆Sons，Ltd.
• Rare and Diverse Binding Modes Introduced through Mechanical Bonding
  作者：David A. Leigh、Paul J. Lusby、Alexandra M. Z. Slawin、D. Barney Walker

  DOI：10.1002/anie.200500004

  日期：2005.7.18
• RASSHOFER W.; OEPEN G.; MUELLER W. M.; VOEGTLE F., CHEM. BER. <CHBE-AM>, 1978, 111, NO 3, 1108-1125
  作者：RASSHOFER W.、 OEPEN G.、 MUELLER W. M.、 VOEGTLE F.

  DOI：——

  日期：——
• Strategies To Reduce hERG K⁺Channel Blockade. Exploring Heteroaromaticity and Rigidity in Novel Pyridine Analogues of Dofetilide
  作者：João F. S. Carvalho、Julien Louvel、Maarten L. J. Doornbos、Elisabeth Klaasse、Zhiyi Yu、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm301564f

  日期：2013.4.11

  Drug-induced blockade of the human ether-a-go-go-related gene K+ channel (hERG) represents one of the major antitarget concerns in pharmaceutical industry. SAR studies of this ion channel have shed light on the structural requirements for hERG interaction but most importantly may reveal drug design principles to reduce hERG affinity. In the present study, a novel library of neutral and positively charged heteroaromatic derivatives of the class III antiarrhythmic agent dofetilide was synthesized and assessed for hERG affinity in radioligand binding and manual patch clamp assays. Structural modifications of the pyridine moiety, side chain, and peripheral aromatic moieties were evaluated, thereby revealing approaches for reducing hERG binding affinity. In particular, we found that the extra rigidity imposed close to the positively charged pyridine moiety can be very efficient in decreasing hERG affinity.
• Kamalov, G. L.; Zakolodyazhnaya, O. V.; Manolova, A. V., Journal of general chemistry of the USSR, 1992, vol. 62, # 3.2, p. 561 - 566
  作者：Kamalov, G. L.、Zakolodyazhnaya, O. V.、Manolova, A. V.、Gavsevich, Yu. V.

  DOI：——

  日期：——