4-[(E)-4-Chloro-phenylimino]-2,3,5-trimethyl-6-(2-methyl-allyl)-cyclohexa-2,5-dienone | 142874-91-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-[(E)-4-Chloro-phenylimino]-2,3,5-trimethyl-6-(2-methyl-allyl)-cyclohexa-2,5-dienone
• 英文别名: 4-(4-Chlorophenylimino)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)-2,5-cyclohexadien-1-one；4-(4-chlorophenyl)imino-2,3,5-trimethyl-6-(2-methylprop-2-enyl)cyclohexa-2,5-dien-1-one
• CAS: 142874-91-7
• 化学式: C₁₉H₂₀ClNO
• 分子量: 313.827
• InChiKey: ICYRPROYDCOXCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-[(E)-4-Chloro-phenylimino]-2,3,5-trimethyl-6-(2-methyl-allyl)-cyclohexa-2,5-dienone 在 sodium dithionite 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 4-(4-Chlorophenylamino)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)phenol
  参考文献：
  名称：

  5-Aminocoumarans:  Dual Inhibitors of Lipid Peroxidation and Dopamine Release with Protective Effects against Central Nervous System Trauma and Ischemia

  摘要：

  A series of 2,3-dihydro-5-benzofuranamines (5-aminocoumarans) were developed for the treatment of traumatic and ischemic central. nervous system (CNS) injury. Compounds within this class were extremely effective inhibitors of lipid peroxidation in vitro and antagonized excitatory behavior coupled with peroxidative injury induced by spinal intrathecal injection of FeCl2 (mouse-FeCl2-it assay) in vivo. Selected compounds were tested for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mouse brain. Among the compounds synthesized, compound 26n (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)meth]-5-benzofuranamine) exhibited potent effects in these assays (inhibition of lipid peroxidation, IC50 = 0.07 mu M; mouse-FeCl2-it assay, ID50 = 10.4 mg/kg, po; MAP-induced hypermotility, 98% inhibition, 10 mg/kg, ip). The S-(+)-form of compound 26n dihydrochloride (TAK-218), which has 30 times more potent antagonistic activity on MAP-induced hypermotility than the R-(-)-form, improved more significantly the survival rate in the cerebral ischemia model (rat, 1-3 mg/kg, ip) during the period of 1-14 days after ischemia and decreased functional disorders in the traumatic brain injury model (rat, 0.1-1 mg/kg, ip) 3-14 days after injury. These results imply a role for dopamine in deterioration of CNS function after ischemic and traumatic injury. TAK-218 is a promising compound for the treatment of stroke and CNS trauma and is now under clinical investigation.

  DOI：

  10.1021/jm960411j
• 作为产物：
  描述：

  2-(2-Methyl-2-propenyl)-3,5,6-trimethylbenzoquinon 、 对氯苯胺 在 吡啶 、 四氯化钛 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.75h， 以96%的产率得到4-[(E)-4-Chloro-phenylimino]-2,3,5-trimethyl-6-(2-methyl-allyl)-cyclohexa-2,5-dienone
  参考文献：
  名称：

  5-Aminocoumarans:  Dual Inhibitors of Lipid Peroxidation and Dopamine Release with Protective Effects against Central Nervous System Trauma and Ischemia

  摘要：

  A series of 2,3-dihydro-5-benzofuranamines (5-aminocoumarans) were developed for the treatment of traumatic and ischemic central. nervous system (CNS) injury. Compounds within this class were extremely effective inhibitors of lipid peroxidation in vitro and antagonized excitatory behavior coupled with peroxidative injury induced by spinal intrathecal injection of FeCl2 (mouse-FeCl2-it assay) in vivo. Selected compounds were tested for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mouse brain. Among the compounds synthesized, compound 26n (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)meth]-5-benzofuranamine) exhibited potent effects in these assays (inhibition of lipid peroxidation, IC50 = 0.07 mu M; mouse-FeCl2-it assay, ID50 = 10.4 mg/kg, po; MAP-induced hypermotility, 98% inhibition, 10 mg/kg, ip). The S-(+)-form of compound 26n dihydrochloride (TAK-218), which has 30 times more potent antagonistic activity on MAP-induced hypermotility than the R-(-)-form, improved more significantly the survival rate in the cerebral ischemia model (rat, 1-3 mg/kg, ip) during the period of 1-14 days after ischemia and decreased functional disorders in the traumatic brain injury model (rat, 0.1-1 mg/kg, ip) 3-14 days after injury. These results imply a role for dopamine in deterioration of CNS function after ischemic and traumatic injury. TAK-218 is a promising compound for the treatment of stroke and CNS trauma and is now under clinical investigation.

  DOI：

  10.1021/jm960411j

文献信息

• Intermediates for pharmaceutically useful aminocoumaran derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05594154A1

  公开（公告）日：1997-01-14

  A novel aminocoumaran derivative of the general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are a hydrogen atom, an acyl group, an alkoxycarbonyl group, an aliphatic group or aromatic group; R.sup.3, R.sup.4 and R.sup.5 are an optionally acylated hydroxyl optionally substituted amino group, alkoxy group or aliphatic group, or two of R.sup.3, R.sup.4 and R.sup.5 may be linked together to form a carbocyclic group; R.sup.6 and R.sup.7 are an aliphatic group and at least one of them has a methylene group at the .alpha.-position; R.sup.8 and R.sup.9 are a hydrogen atom or an aliphatic group or aromatic group, or a salt thereof is useful for medicines for preventing and treating various diseases such as arterial sclerosis, hepatopathy, cerebrovascular diseases and the like.

  一种新型氨基香豆素衍生物的一般式为（I）：##STR1## 其中，R.sup.1和R.sup.2是氢原子、酰基、烷氧羰基、脂肪基或芳基；R.sup.3、R.sup.4和R.sup.5是一个可选酰化的羟基、可选取代的氨基、烷氧基或脂肪基，或R.sup.3、R.sup.4和R.sup.5中的两个可连接在一起形成碳环基；R.sup.6和R.sup.7是脂肪基，其中至少一个在α位上有一个亚甲基；R.sup.8和R.sup.9是氢原子或脂肪基或芳基，或其盐，可用于预防和治疗各种疾病，如动脉硬化、肝病、脑血管疾病等。
• Intermediates for the preparation of aminocoumaran derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05770772A1

  公开（公告）日：1998-06-23

  Disclosed are intermediates for the preparation of novel aminocoumaran derivatives of the general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are a hydrogen atom, an acyl group, an alkoxycarbonyl group, an aliphatic group or aromatic group; R.sup.3, R.sup.4 and R.sup.5 are an optionally acylated hydroxyl, optionally substituted amino group, alkoxy group or aliphatic group, or two of R.sup.3, R.sup.4 and R.sup.5 may be linked together to form a carbocyclic group; R.sup.6 and R.sup.7 are an aliphatic group and at least one of them has a methylene group at the .alpha.-position; R.sup.8 and R.sup.9 are a hydrogen atom or an aliphatic group or aromatic group, or a salt thereof is useful for medicines for preventing and treating various diseases such as arterial sclerosis, hepatopathy, cerebrovascular diseases and the like.

  本发明涉及一种制备新型氨基香豆素衍生物的中间体，其一般式为(I)：##STR1## 其中，R.sup.1和R.sup.2是氢原子、酰基、烷氧羰基、脂肪基或芳香基；R.sup.3、R.sup.4和R.sup.5是可选酰化的羟基、可选取代的氨基、烷氧基或脂肪基，或R.sup.3、R.sup.4和R.sup.5中的两个可以连接在一起形成碳环基；R.sup.6和R.sup.7是脂肪基，其中至少一个在α-位上有一个亚甲基；R.sup.8和R.sup.9是氢原子或脂肪基或芳香基，或其盐，适用于预防和治疗各种疾病，如动脉硬化、肝病、脑血管疾病等。
• 5-Aminocoumarans:  Dual Inhibitors of Lipid Peroxidation and Dopamine Release with Protective Effects against Central Nervous System Trauma and Ischemia
  作者：Shigenori Ohkawa、Kohji Fukatsu、Shokyo Miki、Tadatoshi Hashimoto、Junko Sakamoto、Takayuki Doi、Yasuo Nagai、Tetsuya Aono

  DOI：10.1021/jm960411j

  日期：1997.2.1

  A series of 2,3-dihydro-5-benzofuranamines (5-aminocoumarans) were developed for the treatment of traumatic and ischemic central. nervous system (CNS) injury. Compounds within this class were extremely effective inhibitors of lipid peroxidation in vitro and antagonized excitatory behavior coupled with peroxidative injury induced by spinal intrathecal injection of FeCl2 (mouse-FeCl2-it assay) in vivo. Selected compounds were tested for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mouse brain. Among the compounds synthesized, compound 26n (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)meth]-5-benzofuranamine) exhibited potent effects in these assays (inhibition of lipid peroxidation, IC50 = 0.07 mu M; mouse-FeCl2-it assay, ID50 = 10.4 mg/kg, po; MAP-induced hypermotility, 98% inhibition, 10 mg/kg, ip). The S-(+)-form of compound 26n dihydrochloride (TAK-218), which has 30 times more potent antagonistic activity on MAP-induced hypermotility than the R-(-)-form, improved more significantly the survival rate in the cerebral ischemia model (rat, 1-3 mg/kg, ip) during the period of 1-14 days after ischemia and decreased functional disorders in the traumatic brain injury model (rat, 0.1-1 mg/kg, ip) 3-14 days after injury. These results imply a role for dopamine in deterioration of CNS function after ischemic and traumatic injury. TAK-218 is a promising compound for the treatment of stroke and CNS trauma and is now under clinical investigation.