N⁴,N⁴-diethyl-1-methyl-N¹-[4]pyridyl-butanediyldiamine

• 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: N⁴,N⁴-diethyl-1-methyl-N¹-[4]pyridyl-butanediyldiamine
• 英文别名: N⁴,N⁴-Diaethyl-1-methyl-N¹-[4]pyridyl-butandiyldiamin；1-N,1-N-diethyl-4-N-pyridin-4-ylpentane-1,4-diamine
• 化学式: C₁₄H₂₅N₃
• mdl: MFCD11119463
• 分子量: 235.373
• InChiKey: YWDMGEVSTYEXRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.642
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氯吡啶盐酸盐 、 2-氨基-5-二乙基氨基戊烷 反应 20.0h， 以24%的产率得到N⁴,N⁴-diethyl-1-methyl-N¹-[4]pyridyl-butanediyldiamine
  参考文献：
  名称：

  Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery

  摘要：

  To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N-4-(4-pyridinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N-4-(7-trifluoromethyl-4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N-4-(4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.

  DOI：

  10.1021/jm060736s

文献信息

• Kalthod; Linnell, Quarterly Journal of Pharmacy and Pharmacology, 1948, vol. 21, p. 63,65
  作者：Kalthod、Linnell

  DOI：——

  日期：——
• Rubzow; Klimko, Zhurnal Obshchei Khimii, 1946, vol. 16, p. 1860,1862
  作者：Rubzow、Klimko

  DOI：——

  日期：——
• Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery
  作者：Jianjun Cheng、Ryan Zeidan、Swaroop Mishra、Aijie Liu、Suzie H. Pun、Rajan P. Kulkarni、Gregory S. Jensen、Nathalie C. Bellocq、Mark E. Davis

  DOI：10.1021/jm060736s

  日期：2006.11.1

  To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N-4-(4-pyridinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N-4-(7-trifluoromethyl-4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N-4-(4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.