[4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-aminopropanoate | 853994-08-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-aminopropanoate
• CAS: 853994-08-8
• 化学式: C₂₄H₂₈ClFN₂O₃
• 分子量: 446.949
• InChiKey: UNTUKCUEPKINCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  6

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-methyl-N-octyloctan-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， 以24.3%的产率得到HP-C8 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：

  [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以90.4%的产率得到[4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-aminopropanoate
  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

• [EN] A NANOFORMULATION FOR GLIOMA TREATMENT AND PROCESS FOR ITS PREPARATION THEREOF<br/>[FR] NANOFORMULATION DESTINÉE AU TRAITEMENT DE GLIOMES ET SON PROCÉDÉ DE PRÉPARATION
  申请人：[en]COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

  公开号：WO2022208546A1

  公开（公告）日：2022-10-06

  The present invention describes the development of a novel, tumor epithelial cell and tumor-associated macrophage (TAM)-targeting, blood brain barrier (BBB) crossing glucose-based nanospheres (CSP). More specifically, the present invention discloses a nanoformulation and/or a composition having anticancer activity comprising of carbon nanosphere (CSP) and a sigma receptor targeting ligand (H8) in the ratio of 1: 0.08 to 1: 0.2, a complex prepared thereof, a process for preparation thereof and a kit for delivery of the drug molecule or the formulation or the composition to tumor site.
• 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.