N-(carboxymethyl)-N-butyl-N-methylbutan-1-aminium trifluoroacetate | 1271727-81-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(carboxymethyl)-N-butyl-N-methylbutan-1-aminium trifluoroacetate
• 英文别名: Dibutyl-(carboxymethyl)-methylazanium;2,2,2-trifluoroacetate
• CAS: 1271727-81-1
• 化学式: C₂F₃O₂*C₁₁H₂₄NO₂
• 分子量: 315.333
• InChiKey: ORKSIEOLVXUXSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.42
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  77.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-aminopropanoate 、 N-(carboxymethyl)-N-butyl-N-methylbutan-1-aminium trifluoroacetate 在 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲醇 为溶剂， 反应 48.75h， 以32.7%的产率得到Dibutyl-[2-[[3-[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]oxy-3-oxopropyl]amino]-2-oxoethyl]-methylazanium;chloride
  参考文献：
  名称：

  Structure−Activity Study To Develop Cationic Lipid-Conjugated Haloperidol Derivatives as a New Class of Anticancer Therapeutics

  摘要：

  Haloperidol (HP), a neuroleptic drug, shows high affinity toward sigma receptors (SR). HP and reduced-HP at higher concentration were known to induce apoptosis in SR-overexpressing carcinomas and melanomas. Herein, we report the development of cationic lipid-conjugated haloperidol as a new class of anticancer therapeutics. In comparison to HP, the C-8 carbon chain analogue (HP-C8) showed significantly high, SR-assisted antiproliferative activity against cancer cells via caspase-3-mediated apoptosis and down-regulation of pAkt. Moreover, melanoma tumor aggressiveness in HP-C8-treated mice was significantly lower than that in HP-treated mice. HP-C8 simultaneously reduced Akt-protein level and increased Bax/Bcl-2 ratio in vascular endothelial cells, thereby indicating a possible protein kinase down-regulatory and apoptosis inducing role in tumor-associated vascular cells. In conclusion, we developed sigma receptor-targeting cationic lipid-modified HP derivatives as a promising class of anticancer therapeutic that concurrently affects cancer and tumor environment associated angiogenic vascular cells through induction of apoptosis and Akt protein down-regulation.

  DOI：

  10.1021/jm101530j
• 作为产物：
  描述：

  tert-butyl 2-(dibutylamino)acetate 以 二氯甲烷 为溶剂， 反应 8.25h， 生成 N-(carboxymethyl)-N-butyl-N-methylbutan-1-aminium trifluoroacetate
  参考文献：
  名称：

  Structure−Activity Study To Develop Cationic Lipid-Conjugated Haloperidol Derivatives as a New Class of Anticancer Therapeutics

  摘要：

  Haloperidol (HP), a neuroleptic drug, shows high affinity toward sigma receptors (SR). HP and reduced-HP at higher concentration were known to induce apoptosis in SR-overexpressing carcinomas and melanomas. Herein, we report the development of cationic lipid-conjugated haloperidol as a new class of anticancer therapeutics. In comparison to HP, the C-8 carbon chain analogue (HP-C8) showed significantly high, SR-assisted antiproliferative activity against cancer cells via caspase-3-mediated apoptosis and down-regulation of pAkt. Moreover, melanoma tumor aggressiveness in HP-C8-treated mice was significantly lower than that in HP-treated mice. HP-C8 simultaneously reduced Akt-protein level and increased Bax/Bcl-2 ratio in vascular endothelial cells, thereby indicating a possible protein kinase down-regulatory and apoptosis inducing role in tumor-associated vascular cells. In conclusion, we developed sigma receptor-targeting cationic lipid-modified HP derivatives as a promising class of anticancer therapeutic that concurrently affects cancer and tumor environment associated angiogenic vascular cells through induction of apoptosis and Akt protein down-regulation.

  DOI：

  10.1021/jm101530j

文献信息

• Structure−Activity Study To Develop Cationic Lipid-Conjugated Haloperidol Derivatives as a New Class of Anticancer Therapeutics
  作者：Krishnendu Pal、SubrataKumar Pore、Sutapa Sinha、Rajiv Janardhanan、Debabrata Mukhopadhyay、Rajkumar Banerjee

  DOI：10.1021/jm101530j

  日期：2011.4.14

  Haloperidol (HP), a neuroleptic drug, shows high affinity toward sigma receptors (SR). HP and reduced-HP at higher concentration were known to induce apoptosis in SR-overexpressing carcinomas and melanomas. Herein, we report the development of cationic lipid-conjugated haloperidol as a new class of anticancer therapeutics. In comparison to HP, the C-8 carbon chain analogue (HP-C8) showed significantly high, SR-assisted antiproliferative activity against cancer cells via caspase-3-mediated apoptosis and down-regulation of pAkt. Moreover, melanoma tumor aggressiveness in HP-C8-treated mice was significantly lower than that in HP-treated mice. HP-C8 simultaneously reduced Akt-protein level and increased Bax/Bcl-2 ratio in vascular endothelial cells, thereby indicating a possible protein kinase down-regulatory and apoptosis inducing role in tumor-associated vascular cells. In conclusion, we developed sigma receptor-targeting cationic lipid-modified HP derivatives as a promising class of anticancer therapeutic that concurrently affects cancer and tumor environment associated angiogenic vascular cells through induction of apoptosis and Akt protein down-regulation.