5-[[(4-Methylphenyl)sulfonyl]oxy]-2-pyridinemethanol | 106984-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[[(4-Methylphenyl)sulfonyl]oxy]-2-pyridinemethanol
• 英文别名: [6-(hydroxymethyl)pyridin-3-yl] 4-methylbenzenesulfonate
• CAS: 106984-94-5
• 化学式: C₁₃H₁₃NO₄S
• 分子量: 279.317
• InChiKey: JSTAZPQNGMPFOD-UHFFFAOYSA-N

物化性质

• 沸点：
  475.2±45.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[[(4-Methylphenyl)sulfonyl]oxy]-2-pyridinemethanol 在 manganese(IV) oxide 、 sodium tetrahydroborate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 66.0h， 生成 [6-[(2,2-dimethoxyethylamino)methyl]pyridin-3-yl] 4-methylbenzenesulfonate
  参考文献：
  名称：

  Inhibitors of dopamine .beta.-hydroxylase. 3. Some 1-(pyridylmethyl)imidazole-2-thiones

  摘要：

  The 1-benzylimidazole-2-thione moiety has been previously shown by Kruse et al. to be broadly associated with dopamine beta-hydroxylase (DBH) inhibitory activity both in vitro and in vivo in spontaneously hypertensive rats (SHR). An extension of structure-activity studies to 1-(pyridylmethyl)- and 1-(oxypyridylmethyl)imidazole-2-thiones is reported here in an attempt to exploit the pH differential that exists across the chromaffin vesicle membrane. We hypothesized that the weakly basic pyridyl compounds would diffuse into the acidic vesicles in their neutral forms where protonation and concentration would occur to enhance their in vivo effectiveness as inhibitors. To test this hypothesis, isomeric 2-, 3- and 4-(1-pyridylmethyl)imidazole-2-thiones were synthesized from the appropriate pyridinecarboxaldehydes by reductive alkylation of aminoacetaldehyde dialkyl acetal followed by imidazole-2-thione formation using acidic potassium thiocyanate. Related oxypyridyl compounds were synthesized by first preparing the appropriate aldehyde intermediate followed by conversion to the imidazole-2-thione by the same procedure. The unsubstituted pyridylmethyl compounds showed modest DBH inhibition in vitro but, consistent with a transport-mediated increase in observed potency, showed significant effects in vivo to increase the vascular ratio of dopamine to norepinephrine and to lower blood pressure.

  DOI：

  10.1021/jm00391a008
• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 5-[[(4-Methylphenyl)sulfonyl]oxy]-2-pyridinemethanol
  参考文献：
  名称：

  Inhibitors of dopamine .beta.-hydroxylase. 3. Some 1-(pyridylmethyl)imidazole-2-thiones

  摘要：

  The 1-benzylimidazole-2-thione moiety has been previously shown by Kruse et al. to be broadly associated with dopamine beta-hydroxylase (DBH) inhibitory activity both in vitro and in vivo in spontaneously hypertensive rats (SHR). An extension of structure-activity studies to 1-(pyridylmethyl)- and 1-(oxypyridylmethyl)imidazole-2-thiones is reported here in an attempt to exploit the pH differential that exists across the chromaffin vesicle membrane. We hypothesized that the weakly basic pyridyl compounds would diffuse into the acidic vesicles in their neutral forms where protonation and concentration would occur to enhance their in vivo effectiveness as inhibitors. To test this hypothesis, isomeric 2-, 3- and 4-(1-pyridylmethyl)imidazole-2-thiones were synthesized from the appropriate pyridinecarboxaldehydes by reductive alkylation of aminoacetaldehyde dialkyl acetal followed by imidazole-2-thione formation using acidic potassium thiocyanate. Related oxypyridyl compounds were synthesized by first preparing the appropriate aldehyde intermediate followed by conversion to the imidazole-2-thione by the same procedure. The unsubstituted pyridylmethyl compounds showed modest DBH inhibition in vitro but, consistent with a transport-mediated increase in observed potency, showed significant effects in vivo to increase the vascular ratio of dopamine to norepinephrine and to lower blood pressure.

  DOI：

  10.1021/jm00391a008

文献信息

• Dopamine-beta-hydroxylase inhibitors
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0214740A2

  公开（公告）日：1987-03-18

  Compounds of structure (I) in which Y is H, OH, halogen or C1-4 alkoxy; X is H, halogen, halo C1-4 alkyl, n is 1 to 5 and R is H or C1-4 alkyl and phar- maceu- tically acceptable salts or hydrates thereof, processes fortheir preparation, compositions containing them and their use in therapy.

  结构(I)的化合物 其中 Y 为 H、OH、卤素或 C1-4 烷氧基；X 为 H、卤素、卤代 C1-4 烷基，n 为 1 至 5，R 为 H 或 C1-4 烷基，以及它们的可接受盐或水合物。 及其可接受的盐或水合物、其制备工艺、含有它们的组合物以及它们在治疗中的用途。
• 4-Anilino-7-pyridyl-3-quinolinecarbonitriles as Src kinase inhibitors
  作者：Nan Zhang、Biqi Wu、Diane H. Boschelli、Jennifer M. Golas、Frank Boschelli

  DOI：10.1016/j.bmcl.2009.07.043

  日期：2009.9

  A series of 4-anilino-7-pyridyl-3-quinolinecarbonitriles was prepared as Src kinase inhibitors. A systematic SAR study of substitutions on both the pyridine ring and the 3-quinolinecarbonitrile core established the requirements for optimal activity. The lead compound, 17, showed potent activity in both the Src enzyme assay and cell assays, and demonstrated in vivo anti-tumor activity in a xenograft model. (C) 2009 Elsevier Ltd. All rights reserved.
• ROSS, S. T.;KRUSE, L. I.;OHLSTEIN, E. H.;ERICKSON, R. W.;EZEKIEL, M.;FLAI+, J. MED. CHEM., 30,(1987) N 8, 1309-1313
  作者：ROSS, S. T.、KRUSE, L. I.、OHLSTEIN, E. H.、ERICKSON, R. W.、EZEKIEL, M.、FLAI+

  DOI：——

  日期：——
• KAISER, CARL;KRUSE, LAWRENCE;ROSS, STEPHEN T.
  作者：KAISER, CARL、KRUSE, LAWRENCE、ROSS, STEPHEN T.

  DOI：——

  日期：——
• US4634711A
  申请人：——

  公开号：US4634711A

  公开（公告）日：1987-01-06