[4-(4-Chloro-phenyl)-piperazin-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)-methanone | 122003-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [4-(4-Chloro-phenyl)-piperazin-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)-methanone
• 英文别名: [4-(4-Chlorophenyl)piperazin-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methanone
• CAS: 122003-24-1
• 化学式: C₂₄H₂₉ClN₂O₃
• 分子量: 428.959
• InChiKey: FTQCIERHWNMELO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-(4-Chloro-phenyl)-piperazin-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)-methanone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以27%的产率得到2-[4-(4-Chloro-phenyl)-piperazin-1-ylmethyl]-2,5,7,8-tetramethyl-chroman-6-ol
  参考文献：
  名称：

  2-(Aminomethyl)chromans that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma and ischemia

  摘要：

  A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron-dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 muM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230 % of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage.

  DOI：

  10.1021/jm00101a025
• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 在 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 17.0h， 生成 [4-(4-Chloro-phenyl)-piperazin-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)-methanone
  参考文献：
  名称：

  Synthesis and anti-inflammatory activity of N-(aza)arylcarboxamides derived from Trolox®

  摘要：

  A series of 6-(aza) arylmethoxychroman-2-carboxamides 22-38, derived from Trolox(R) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, was prepared using two strategies, i.e. phenol blockade was carried out before or after amidification. These compounds were evaluated against peripheral inflammation by a carrageenin-induced foot-pad edema test. A permanent blockade of the phenol function by arylmethoxy groupings, in particular by the quinolylmethoxy moiety, was generally detrimental to activity; only the 6-benzyloxy and quinolylmethoxy derivatives 22 and 31 exhibited significant inhibition (58.3 and 97.1%) after oral administration of 0.4 mmol kg(-1). Among their 6-acetoxy or 6-hydroxy precursors 12-21, evaluated at 0.4 and 0.1 mmol kg(-1), the N-(4-pyridyl) chromancarboxamides 15 and 20 exerted the highest inhibitory activity. Their ID50 were 14.7 +/- 5.5 mg kg(-1) and 14.7 +/- 4.5 mg kg(-1), respectively. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80065-2

文献信息

• Pharmaceutically active amines
  申请人：THE UPJOHN COMPANY

  公开号：EP0293078A1

  公开（公告）日：1988-11-30

  The aromatic amines (I), alkyl amines (II), bicyclic amines (III), cycloalkyl amines (IV), aromatic bicyclic amines (V), hydroquinone amines (VI), quinone amines (VII), amino-ethers (VIII) and bicyclic amino ethers (IX) are useful as pharmaceutical agents for treating a number of conditions including spinal trauma, mild and/or moderate to severe head injury, etc. Also dislosed is a method of treatment using the 3,4-dihydrobenzopyrans (XI).

  芳香胺 (I)、烷基胺 (II)、双环胺 (III) 环烷基胺 (IV)、芳香族双环胺 (V)、对苯二酚胺 (VI)、醌胺 (VII)、氨基醚 (VIII) 和双环氨基醚 (IX) 可用作治疗多种疾病的药物，包括脊柱创伤、轻度和/或中重度头部损伤等。此外，还公开了一种使用 3,4-二氢苯并吡喃（XI）的治疗方法。
• PHARMACEUTICALLY ACTIVE AMINES
  申请人：THE UPJOHN COMPANY

  公开号：EP0358676A1

  公开（公告）日：1990-03-21
• [EN] PHARMACEUTICALLY ACTIVE AMINES
  申请人：THE UPJOHN COMPANY

  公开号：WO1988008424A1

  公开（公告）日：1988-11-03

  (EN) The aromatic amines (I), alkyl amines (II), bicyclic amines (III), cycloalkyl amines (IV), aromatic bicyclic amines (V), hydroquinone amines (VI), quinone amines (VII), amino-ethers (VIII) and bicyclic amino ethers (IX) are useful as pharmaceutical agents for treating a number of conditions including spinal trauma, mild and/or moderate to severe head injury, etc. Also disclosed is a method of treatment using the 3,4-dihydrobenzopyrans (XI).(FR) Les amines aromatiques (I), les alkylamines (II), les amines bicycliques (III), les cycloalkylamines (IV), les amines bicycliques aromatiques (V), les amines d'hydroquinone (VI), les amines de quinone (VII), les amino-éthers (VIII) et les amino-éthers bicycliques (IX) sont utiles en tant qu'agents pharmaceutiques pour traiter plusieurs états pathologiques, entre autres les traumas de la moelle épinière, et les blessures à la tête légères et/ou modérées à graves, etc. Une méthode de traitement utilisant 3,4-dihydrobenzopyranes (XI) est également décrite.
• 2-(Aminomethyl)chromans that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma and ischemia
  作者：E. Jon Jacobsen、Fred J. VanDoornik、Donald E. Ayer、Kenneth L. Belonga、J. Mark Braughler、Edward D. Hall、David J. Houser

  DOI：10.1021/jm00101a025

  日期：1992.11

  A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron-dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 muM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230 % of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage.
• Synthesis and anti-inflammatory activity of N-(aza)arylcarboxamides derived from Trolox®
  作者：Claudie Moulin、Muriel Duflos、Guillaume Le Baut、Nicole Grimaud、Pierre Renard、Daniel-Henri Caignard

  DOI：10.1016/s0223-5234(98)80065-2

  日期：1998.4

  A series of 6-(aza) arylmethoxychroman-2-carboxamides 22-38, derived from Trolox(R) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, was prepared using two strategies, i.e. phenol blockade was carried out before or after amidification. These compounds were evaluated against peripheral inflammation by a carrageenin-induced foot-pad edema test. A permanent blockade of the phenol function by arylmethoxy groupings, in particular by the quinolylmethoxy moiety, was generally detrimental to activity; only the 6-benzyloxy and quinolylmethoxy derivatives 22 and 31 exhibited significant inhibition (58.3 and 97.1%) after oral administration of 0.4 mmol kg(-1). Among their 6-acetoxy or 6-hydroxy precursors 12-21, evaluated at 0.4 and 0.1 mmol kg(-1), the N-(4-pyridyl) chromancarboxamides 15 and 20 exerted the highest inhibitory activity. Their ID50 were 14.7 +/- 5.5 mg kg(-1) and 14.7 +/- 4.5 mg kg(-1), respectively. (C) Elsevier, Paris.