2-Methyl-2-(2,4,5-trimethoxy-phenyl)-propionitrile | 60059-04-3

• 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: 2-Methyl-2-(2,4,5-trimethoxy-phenyl)-propionitrile
• 英文别名: 2-Methyl-2-(2,4,5-trimethoxyphenyl)propanenitrile；2-methyl-2-(2,4,5-trimethoxyphenyl)propanenitrile
• CAS: 60059-04-3
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: NPWQFSWLZNYRCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Methyl-2-(2,4,5-trimethoxy-phenyl)-propionitrile 在 lithium aluminium tetrahydride 、 三氯化铝 作用下， 以 乙醚 为溶剂， 生成 2-Methyl-2-(2,4,5-trimethoxy-phenyl)-propylamine
  参考文献：
  名称：

  Catechol O-methyltransferase. 9. Mechanism of inactivation by 6-hydroxydopamine

  摘要：

  A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared had methyl groups incorporated in the 2 and/or 5 positions of 6-OHDA so as to block nucleophilic attakc at these positions in the corresponding oxidation products [6-hydroxydopamine-p-quinone (6-OHDAQ), aminochromes I and II]. Such 2- and/or 5-methylated 6-OHDA analogues were found to be inhibitors of COMT with the inactivation apparently resulting from modification of an essential amino acid residue at the active site of the enzyme. The activity of these analogues as inhibitors of COMT argues against a mechanism involving a 1,4 Michael addition reaction by a protein nucleophile at the 2 or 5 positions on 6-OHDAQ or on the corresponding aminochromes. Instead, an alternative mechanism is proposed to explain these data, which involves attack of a protein nucleophile at the carbonyl group in the 6 position of 6-OHDAQ or at the imine functionality on aminochromes I and II. The results of the present experiments have provided insight into the mechanism involved in inactivation of COMT by 6-OHDA. In addition, this study has provided considerable insight into the chemical reactivity of the electrophilic species generated after oxidation of 6-OHDA.

  DOI：

  10.1021/jm00232a007
• 作为产物：
  描述：

  2,4,5-trimethoxybenzeneacetonitrile 、 碘甲烷 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 生成 2-Methyl-2-(2,4,5-trimethoxy-phenyl)-propionitrile
  参考文献：
  名称：

  Catechol O-methyltransferase. 9. Mechanism of inactivation by 6-hydroxydopamine

  摘要：

  A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared had methyl groups incorporated in the 2 and/or 5 positions of 6-OHDA so as to block nucleophilic attakc at these positions in the corresponding oxidation products [6-hydroxydopamine-p-quinone (6-OHDAQ), aminochromes I and II]. Such 2- and/or 5-methylated 6-OHDA analogues were found to be inhibitors of COMT with the inactivation apparently resulting from modification of an essential amino acid residue at the active site of the enzyme. The activity of these analogues as inhibitors of COMT argues against a mechanism involving a 1,4 Michael addition reaction by a protein nucleophile at the 2 or 5 positions on 6-OHDAQ or on the corresponding aminochromes. Instead, an alternative mechanism is proposed to explain these data, which involves attack of a protein nucleophile at the carbonyl group in the 6 position of 6-OHDAQ or at the imine functionality on aminochromes I and II. The results of the present experiments have provided insight into the mechanism involved in inactivation of COMT by 6-OHDA. In addition, this study has provided considerable insight into the chemical reactivity of the electrophilic species generated after oxidation of 6-OHDA.

  DOI：

  10.1021/jm00232a007

文献信息

• Catechol O-methyltransferase. 9. Mechanism of inactivation by 6-hydroxydopamine
  作者：R. T. Borchardt、J. R. Reid、D. R. Thakker、Y. O. Liang、R. W. Wightman、R. N. Adams

  DOI：10.1021/jm00232a007

  日期：1976.10

  A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared had methyl groups incorporated in the 2 and/or 5 positions of 6-OHDA so as to block nucleophilic attakc at these positions in the corresponding oxidation products [6-hydroxydopamine-p-quinone (6-OHDAQ), aminochromes I and II]. Such 2- and/or 5-methylated 6-OHDA analogues were found to be inhibitors of COMT with the inactivation apparently resulting from modification of an essential amino acid residue at the active site of the enzyme. The activity of these analogues as inhibitors of COMT argues against a mechanism involving a 1,4 Michael addition reaction by a protein nucleophile at the 2 or 5 positions on 6-OHDAQ or on the corresponding aminochromes. Instead, an alternative mechanism is proposed to explain these data, which involves attack of a protein nucleophile at the carbonyl group in the 6 position of 6-OHDAQ or at the imine functionality on aminochromes I and II. The results of the present experiments have provided insight into the mechanism involved in inactivation of COMT by 6-OHDA. In addition, this study has provided considerable insight into the chemical reactivity of the electrophilic species generated after oxidation of 6-OHDA.