(6-phenylpyridine-2,4-diyl)dimethanol | 172799-94-9

• 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: (6-phenylpyridine-2,4-diyl)dimethanol
• 英文别名: 6-phenyl-2,4-pyridinemethanol；6-Phenyl-2,4-pyridinedimethanol；[2-(hydroxymethyl)-6-phenylpyridin-4-yl]methanol
• CAS: 172799-94-9
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: QEUCSFFHCZSTEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  53.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6-phenylpyridine-2,4-diyl)dimethanol 在 氢溴酸 作用下， 以 乙酸酐 为溶剂， 以47%的产率得到6-phenyl-2,4-bis(bromomethyl)pyridine hydrobromide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-tetraazamacrocycles That Inhibit Human Immunodeficiency Virus Replication. 2. Effect of Heteroaromatic Linkers on the Activity of Bicyclams

  摘要：

  A series of bicyclam analogs connected through a heteroaromatic linker have been synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2 (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked bicyclams was found to be highly dependent upon the substitution of the heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5-pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication, whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited substantially reduced activity and, in addition, were found to be highly toxic to MT-4 cells. We have subsequently discovered that these effects are not unique; amino-substituted linkers also have the potential to deactivate phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the deactivating effects of the pyridine group in certain substitution patterns based on the ability of the pyridine nitrogen to participate in pendant conformations (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen bonding or coordination to a transition metal. The introduction of a sterically hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine-linked bicyclam appears to prevent pendant conformations, providing an analog with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m-phenylenebis(methylene)-linked bicyclam, The results of this study have been used to develop a quantitative structure-activity relationship model with improved predictive capability in order to aid the design of antiviral bis-azamacrocyclic analogs.

  DOI：

  10.1021/jm950584t
• 作为产物：
  描述：

  2-溴-4,6-二甲基吡啶 在 potassium permanganate 、 四(三苯基膦)钯 、 硼烷四氢呋喃络合物 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 、 叔丁醇 为溶剂， 生成 (6-phenylpyridine-2,4-diyl)dimethanol
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-tetraazamacrocycles That Inhibit Human Immunodeficiency Virus Replication. 2. Effect of Heteroaromatic Linkers on the Activity of Bicyclams

  摘要：

  A series of bicyclam analogs connected through a heteroaromatic linker have been synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2 (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked bicyclams was found to be highly dependent upon the substitution of the heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5-pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication, whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited substantially reduced activity and, in addition, were found to be highly toxic to MT-4 cells. We have subsequently discovered that these effects are not unique; amino-substituted linkers also have the potential to deactivate phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the deactivating effects of the pyridine group in certain substitution patterns based on the ability of the pyridine nitrogen to participate in pendant conformations (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen bonding or coordination to a transition metal. The introduction of a sterically hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine-linked bicyclam appears to prevent pendant conformations, providing an analog with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m-phenylenebis(methylene)-linked bicyclam, The results of this study have been used to develop a quantitative structure-activity relationship model with improved predictive capability in order to aid the design of antiviral bis-azamacrocyclic analogs.

  DOI：

  10.1021/jm950584t

文献信息

• Pyridines via solid-supported [2 + 2 + 2] cyclotrimerization
  作者：Ramesh S. Senaiar、Douglas D. Young、Alexander Deiters

  DOI：10.1039/b515901f

  日期：——

  The formation of pyridines via a crossed [2 + 2 + 2] cycloaddition has been achieved on a solid-support for the first time.

  通过交叉的[2 + 2 + 2]环加成反应首次在固体载体上形成吡啶。
• Photoredox-Catalyzed Hydroxymethylation of Heteroaromatic Bases
  作者：Chelsea A. Huff、Ryan D. Cohen、Kevin D. Dykstra、Eric Streckfuss、Daniel A. DiRocco、Shane W. Krska

  DOI：10.1021/acs.joc.6b00811

  日期：2016.8.19

  We report the development of a method for room-temperature C–H hydroxymethylation of heteroarenes. A key enabling advance in this work was achieved by implementing visible light photoredox catalysis that proved to be applicable to many classes of heteroarenes and tolerant of diverse functional groups found in druglike molecules.

  我们报告了杂芳烃室温C–H羟甲基化方法的发展。这项工作取得了关键的进展，这是通过实施可见光光氧化还原催化来实现的，该催化被证明适用于多种类别的杂芳烃，并能耐受类药物分子中发现的各种官能团。
• Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-tetraazamacrocycles That Inhibit Human Immunodeficiency Virus Replication. 2. Effect of Heteroaromatic Linkers on the Activity of Bicyclams
  作者：Gary J. Bridger、Renato T. Skerlj、Sreenivasan Padmanabhan、Stephen A. Martellucci、Geoffrey W. Henson、Michael J. Abrams、Heidi C. Joao、Myriam Witvrouw、Karen De Vreese、Rudi Pauwels、Erik De Clercq

  DOI：10.1021/jm950584t

  日期：1996.1.1

  A series of bicyclam analogs connected through a heteroaromatic linker have been synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2 (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked bicyclams was found to be highly dependent upon the substitution of the heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5-pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication, whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited substantially reduced activity and, in addition, were found to be highly toxic to MT-4 cells. We have subsequently discovered that these effects are not unique; amino-substituted linkers also have the potential to deactivate phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the deactivating effects of the pyridine group in certain substitution patterns based on the ability of the pyridine nitrogen to participate in pendant conformations (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen bonding or coordination to a transition metal. The introduction of a sterically hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine-linked bicyclam appears to prevent pendant conformations, providing an analog with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m-phenylenebis(methylene)-linked bicyclam, The results of this study have been used to develop a quantitative structure-activity relationship model with improved predictive capability in order to aid the design of antiviral bis-azamacrocyclic analogs.