1-(4-吡啶基甲基)-1,3-二氢-2H-咪唑-2-硫酮 | 106984-87-6

• 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
• 中文名称: 1-(4-吡啶基甲基)-1,3-二氢-2H-咪唑-2-硫酮
• 英文名称: 1-(4-pyridylmethyl)-1,3-dihydro-2H-imidazole-2-thione
• 英文别名: 3-(pyridin-4-ylmethyl)-1H-imidazole-2-thione
• CAS: 106984-87-6
• 化学式: C₉H₉N₃S
• 分子量: 191.257
• InChiKey: DKWUDHGPWNSMCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  potassium thioacyanate 、 (2,2-Dimethoxy-ethyl)-pyridin-4-ylmethyl-amine; hydrochloride 在 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 以83%的产率得到1-(4-吡啶基甲基)-1,3-二氢-2H-咪唑-2-硫酮
  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

• 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：——
• Inhibitors of dopamine .beta.-hydroxylase. 3. Some 1-(pyridylmethyl)imidazole-2-thiones
  作者：Stephen T. Ross、Lawrence I. Kruse、Eliot H. Ohlstein、Robert W. Erickson、Mildred Ezekiel、Kathryn E. Flaim、John L. Sawyer、Barry A. Berkowitz

  DOI：10.1021/jm00391a008

  日期：1987.8

  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.