YT-15 | 142874-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: YT-15
• 英文别名: 2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine；5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran；2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-amine；2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-amine
• CAS: 142874-28-0
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: LMFDBZWAXNOMNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  YT-15 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 48.5h， 生成 YT-14
  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：

  N-[4-hydroxy-2,3,6-trimethyl-5-(2-methyl-2-propenyl)phenyl]formamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以99%的产率得到YT-15
  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

• Benzofuran derivatives
  申请人：Tsukamoto Tetsuya

  公开号：US20100234357A1

  公开（公告）日：2010-09-16

  The present invention provides a compound represented by the following formula (I): wherein: Ring A represents an optionally substituted piperazine ring, an optionally substituted morpholine ring, or an optionally substituted homopiperazine ring; R 1 and R 2 are the same or different from each other, and represent a hydrogen atom or optionally substituted lower alkyl; R 3 and R 4 are the same or different from each other, and represent a hydrogen atom or halogenated or non-halogenated lower alkyl; R 5 to R 7 are the same or different from each other, and represent a hydrogen atom, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic ring, optionally substituted amino, or acyl; and represents a single bond or double bond, or a salt thereof.

  本发明提供了一种由以下式（I）表示的化合物： 其中： 环A代表可选择地取代的哌嗪环、可选择地取代的吗啉环或可选择地取代的同环丙二胺环； R1和R2彼此相同或不同，代表氢原子或可选择地取代的较低烷基； R3和R4彼此相同或不同，代表氢原子或卤代或非卤代的较低烷基； R5到R7彼此相同或不同，代表氢原子、羟基、可选择地取代的较低烷基、可选择地取代的较低烯基、可选择地取代的较低烷氧基、可选择地取代的环烷基、可选择地取代的芳基、可选择地取代的芳香杂环、可选择地取代的氨基或酰基；和 代表单键或双键，或其盐。
• Aminocoumaran derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05376681A1

  公开（公告）日：1994-12-27

  A 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 schleosis, hepatopathy, cerebrovascular diseases and the like.

  一种一般式（I）的新型氨基香豆素衍生物：##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，或者R.sup.3、R.sup.4和R.sup.5中的两个可以连接在一起形成一个碳环基团；R.sup.6和R.sup.7是脂肪基，其中至少一个在α-位置有一个亚甲基基团；R.sup.8和R.sup.9是氢原子或脂肪基或芳香基，或其盐，用于预防和治疗各种疾病，如动脉硬化、肝病、脑血管疾病等。
• Benzofuran derivatives, their production and use
  申请人：——

  公开号：US20020160996A1

  公开（公告）日：2002-10-31

  Compounds represented by the formula: 1 wherein R 1 and R 2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R 1 and R 2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula: 2 wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula: 3 wherein R 4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R 5 is hydrogen atom, a C 1-6 alkyl, or an acyl group, provided that, when W is Wa, R 3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R 3 indicates a C 6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

  由以下公式代表的化合物： 其中 R1 和 R2 是氢原子、烃基或杂环基，或者 R1 和 R2 可以与相邻的碳原子一起形成 3 至 8 个成员的同环或杂环环，W 表示 (i) 由以下公式代表的基团： 其中环 B 表示一个 5 至 7 个成员的环，或者 (ii) 由以下公式代表的基团： 其中 R4 表示 (1) 可以用芳香基取代的脂肪烃基，或者 (2) 含有芳香基的酰基，R5 是氢原子、C1-6 烷基或酰基，提供当 W 是 Wa 时，R3 是氢原子、烃基或杂环基，当 W 是 Wb 时，R3 表示一个 C6-14 芳基，或其盐或前药具有优异的抑制神经退行性等作用，以及出色的脑透过性，毒性低，因此可用作预防或治疗神经退行性疾病等的药物。
• 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。
• Method of using aminocoumaran derivatives for treating cerebrovascular
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05478844A1

  公开（公告）日：1995-12-26

  A 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 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，其通式为(I)：##STR1## 其中R.sup.1和R.sup.2为氢原子、酰基、烷氧基羰基、脂肪基或芳香族基；R.sup.3、R.sup.4和R.sup.5为可选的酰化羟基、可选的取代氨基、烷氧基或脂肪基，或者R.sup.3、R.sup.4和R.sup.5中的两个可以连接在一起形成一个环状碳骨架；R.sup.6和R.sup.7为脂肪基，至少其中一个在α-位上有一个亚甲基；R.sup.8和R.sup.9为氢原子、脂肪基或芳香族基，或其盐，用于治疗各种疾病，如动脉硬化、肝病、脑血管疾病等。