(4-(4-(6-chloro-2-methoxyacridin-9-ylamino)phenyl)piperazin-1-yl)(cyclohexyl)methanone | 1594853-50-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (4-(4-(6-chloro-2-methoxyacridin-9-ylamino)phenyl)piperazin-1-yl)(cyclohexyl)methanone
• 英文别名: (4-(4-(6-chloro-2-methoxyacridin-9-ylamino)phenyl)piperazin-1-yl)(phenyl)methanone；[4-[4-[(6-Chloro-2-methoxyacridin-9-yl)amino]phenyl]piperazin-1-yl]-phenylmethanone；[4-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]phenyl]piperazin-1-yl]-phenylmethanone
• CAS: 1594853-50-5
• 化学式: C₃₁H₂₇ClN₄O₂
• 分子量: 523.034
• InChiKey: NBFVRRYLYJXXMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-苯甲酰哌嗪 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 120.0 ℃ 、344.75 kPa 条件下， 反应 24.0h， 生成 (4-(4-(6-chloro-2-methoxyacridin-9-ylamino)phenyl)piperazin-1-yl)(cyclohexyl)methanone
  参考文献：
  名称：

  Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species

  摘要：

  The in vitro neuronal cell death model based on the HT22 mouse hippocampal cell model is a convenient means of identifying compounds that protect against oxidative glutamate toxicity which plays a role in the development of certain neurodegenerative diseases. Functionalized acridin-9-yl-phenylamines were found to protect HT22 cells from glutamate challenge at submicromolar concentrations. The Aryl(1)-NH-Aryl(2) scaffold that is embedded in these compounds was the minimal pharmacophore for activity. Mechanistically, protection against the endogenous oxidative stress generated by glutamate did not involve up-regulation of glutathione levels but attenuation of the late stage increases in mitochondrial ROS and intracellular calcium levels. The NH residue in the pharmacophore played a crucial role in this regard as seen from the loss of neuroprotection when it was structurally modified or replaced. That the same NH was essential for radical scavenging in cell-free and cell-based systems pointed to an antioxidant basis for the neuroprotective activities of these compounds. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.006

文献信息

• Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species
  作者：Thuy Nguyen、Tianming Yang、Mei-Lin Go

  DOI：10.1016/j.bmcl.2014.02.006

  日期：2014.4

  The in vitro neuronal cell death model based on the HT22 mouse hippocampal cell model is a convenient means of identifying compounds that protect against oxidative glutamate toxicity which plays a role in the development of certain neurodegenerative diseases. Functionalized acridin-9-yl-phenylamines were found to protect HT22 cells from glutamate challenge at submicromolar concentrations. The Aryl(1)-NH-Aryl(2) scaffold that is embedded in these compounds was the minimal pharmacophore for activity. Mechanistically, protection against the endogenous oxidative stress generated by glutamate did not involve up-regulation of glutathione levels but attenuation of the late stage increases in mitochondrial ROS and intracellular calcium levels. The NH residue in the pharmacophore played a crucial role in this regard as seen from the loss of neuroprotection when it was structurally modified or replaced. That the same NH was essential for radical scavenging in cell-free and cell-based systems pointed to an antioxidant basis for the neuroprotective activities of these compounds. (C) 2014 Elsevier Ltd. All rights reserved.