2-methyl-8-amino-4-azaoctanenitrile | 1310077-79-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-methyl-8-amino-4-azaoctanenitrile
• 英文别名: 3-(4-Aminobutylamino)-2-methylpropanenitrile
• CAS: 1310077-79-2
• 化学式: C₈H₁₇N₃
• 分子量: 155.243
• InChiKey: UMXAIAYAPRHXTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-8-amino-4-azaoctanenitrile 以 1,4-二氧六环 为溶剂， 反应 102.0h， 生成 N⁴,N⁹-bis-(tert-butyloxycarbonyl)-2,11-dimethyl-4,9-diazadodecane-1,12-dinitrile
  参考文献：
  名称：

  研究新型C-甲基化精胺衍生物揭示的多胺代谢调控的不可预见的可能性。

  摘要：

  生物多胺，精胺（Spm）和亚精胺是参与参与重要细胞功能（包括增殖和分化）调节的所有真核细胞中以毫摩尔浓度存在的有机聚阳离子。多胺类似物的设计和生化评估是多胺研究的基础。在这里，我们合成和研究了新颖的C-甲基化Spm类似物：2,11-二甲基精胺（2,11-Me2Spm），3,10-二甲基精胺（3,10-Me2Spm），2-甲基精胺和2,2-二甲基精胺。所测试的类似物克服了鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸72 h诱导的生长停滞，并通过多胺转运蛋白进入DU145细胞。3，与2,11-Me2Spm相比，10-Me2Spm是精胺氧化酶和亚精胺/亚精胺-N1-乙酰基转移酶（SSAT）的较差底物，因此类似于1,12-二甲基精胺，它缺少SSAT反应所需的底物性质。由抗酶（OAZ1）介导的ODC下调和多胺转运的抑制对于维持多胺体内稳态至关重要。有趣的是，发现3,10-Me2Spm是第一个不会诱

  DOI：

  10.1021/acs.jmedchem.9b01666
• 作为产物：
  描述：

  四亚甲基二胺 、 甲基丙烯腈 以 乙醇 为溶剂， 反应 6.5h， 以47%的产率得到2-methyl-8-amino-4-azaoctanenitrile
  参考文献：
  名称：

  The Use of Novel C-Methylated Spermidine Derivatives To Investigate the Regulation of Polyamine Metabolism

  摘要：

  The polyamines are organic polycations present at millimolar concentrations in eukaryotic cells where they participate in the regulation of vital cellular functions including proliferation and differentiation. Biological evaluation of rationally designed polyamine analogs is one of the cornerstones of polyamine research. Here we have synthesized and characterized novel C-methylated spermidine analogs, that is, 2-methylspermidine, 3-methylspermidine, and 8-methylspermidine. 3-Methylspermidine was found to be metabolically stable in DU145 cells, while 8-methylspermidine was a substrate for spermidine/spermine N(1)-acetyltransferase (SSAT) and 2-methylspermidine was a substrate for both SSAT and acetylpolyamine oxidase. All the analogs induced the splicing of the productive mRNA splice variant of SSAT, overcame growth arrest induced by 72-h treatment with ornithine decarboxylase (ODC), inhibitor alpha-difluoromethylornithine, and were transported via the poly amine transporter. Surprisingly, 2-methylspermidine was a weak downregulator of ODC activity in DU145 cells. Our data demonstrates that it is possible to radically alter the biochemical properties of a polyamine analog by changing the position of the methyl group.

  DOI：

  10.1021/jm200293r

文献信息

• The Use of Novel C-Methylated Spermidine Derivatives To Investigate the Regulation of Polyamine Metabolism
  作者：Mervi T. Hyvönen、Tuomo A. Keinänen、Maxim Khomutov、Alina Simonian、Janne Weisell、Sergey N. Kochetkov、Jouko Vepsäläinen、Leena Alhonen、Alex R. Khomutov

  DOI：10.1021/jm200293r

  日期：2011.7.14

  The polyamines are organic polycations present at millimolar concentrations in eukaryotic cells where they participate in the regulation of vital cellular functions including proliferation and differentiation. Biological evaluation of rationally designed polyamine analogs is one of the cornerstones of polyamine research. Here we have synthesized and characterized novel C-methylated spermidine analogs, that is, 2-methylspermidine, 3-methylspermidine, and 8-methylspermidine. 3-Methylspermidine was found to be metabolically stable in DU145 cells, while 8-methylspermidine was a substrate for spermidine/spermine N(1)-acetyltransferase (SSAT) and 2-methylspermidine was a substrate for both SSAT and acetylpolyamine oxidase. All the analogs induced the splicing of the productive mRNA splice variant of SSAT, overcame growth arrest induced by 72-h treatment with ornithine decarboxylase (ODC), inhibitor alpha-difluoromethylornithine, and were transported via the poly amine transporter. Surprisingly, 2-methylspermidine was a weak downregulator of ODC activity in DU145 cells. Our data demonstrates that it is possible to radically alter the biochemical properties of a polyamine analog by changing the position of the methyl group.
• Unforeseen Possibilities To Investigate the Regulation of Polyamine Metabolism Revealed by Novel C-Methylated Spermine Derivatives
  作者：Maxim Khomutov、Mervi T. Hyvönen、Alina Simonian、Andrey A. Formanovsky、Irina V. Mikhura、Alexander O. Chizhov、Sergey N. Kochetkov、Leena Alhonen、Jouko Vepsäläinen、Tuomo A. Keinänen、Alex R. Khomutov

  DOI：10.1021/acs.jmedchem.9b01666

  日期：2019.12.26

  The biogenic polyamines, spermine (Spm) and spermidine, are organic polycations present in millimolar concentrations in all eukaryotic cells participating in the regulation of vital cellular functions including proliferation and differentiation. The design and biochemical evaluation of polyamine analogues are cornerstones of polyamine research. Here we synthesized and studied novel C-methylated Spm

  生物多胺，精胺（Spm）和亚精胺是参与参与重要细胞功能（包括增殖和分化）调节的所有真核细胞中以毫摩尔浓度存在的有机聚阳离子。多胺类似物的设计和生化评估是多胺研究的基础。在这里，我们合成和研究了新颖的C-甲基化Spm类似物：2,11-二甲基精胺（2,11-Me2Spm），3,10-二甲基精胺（3,10-Me2Spm），2-甲基精胺和2,2-二甲基精胺。所测试的类似物克服了鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸72 h诱导的生长停滞，并通过多胺转运蛋白进入DU145细胞。3，与2,11-Me2Spm相比，10-Me2Spm是精胺氧化酶和亚精胺/亚精胺-N1-乙酰基转移酶（SSAT）的较差底物，因此类似于1,12-二甲基精胺，它缺少SSAT反应所需的底物性质。由抗酶（OAZ1）介导的ODC下调和多胺转运的抑制对于维持多胺体内稳态至关重要。有趣的是，发现3,10-Me2Spm是第一个不会诱