N-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenylmethyl)-acetamide

• 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: N-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenylmethyl)-acetamide
• 英文别名: N-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenylmethyl)acetamide；N-{4-[4-(4-Fluoro-phenyl)-piperazin-1-ylmethyl]-benzyl}-acetamide；N-[[4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]phenyl]methyl]acetamide
• 化学式: C₂₀H₂₄FN₃O
• 分子量: 341.428
• InChiKey: ILPWPSSBNJOSQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氨甲基苯甲酸 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 硫酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-((4-(4-fluorophenyl)piperazin-1-yl)methyl)phenylmethyl)-acetamide
  参考文献：
  名称：

  Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity

  摘要：

  Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice, suggesting that 5k would be a promising drug candidate for the treatment of TNF-alpha associated diseases including septic shock. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00128-1

文献信息

• Piperazine compounds and medicinal use thereof
  申请人：Mitsubishi Pharma Corporation

  公开号：US06455528B1

  公开（公告）日：2002-09-24

  The present invention relates to a piperazine compound of the formula wherein R1 and R2 are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4 and R5 are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6 and R7 are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8 and R9 are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-&agr; production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-&agr; production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-&agr; production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-&agr; mediated diseases.

  本发明涉及一种哌嗪化合物，其化学式为 其中R1和R2分别为氢、卤素、低烷基、低烷氧基、氨基、取代氨基、硝基、羟基或氰基，R3、R4和R5分别为氢、卤素、低烷基、低烷氧基、硝基、氨基、取代氨基或羟基，R6和R7分别为氢、低烷基、受卤素取代的低烷基、芳基烷基、酰基或受卤素取代的低酰基，R8和R9分别为氢或低烷基，Y为低烷基烯基等，环A为苯基、嘧啶基、噻唑基、吡啶基、吡啉基或咪唑基，其药学上可接受的盐及含有这些化合物的药物制剂。本发明的化合物具有优越的TNF-α产生抑制作用和/或IL-10产生促进作用，由于它不含或仅显示对中枢神经系统有显著减少的作用，该化合物可用作高度安全和优越的TNF-α产生抑制剂和/或IL-10产生促进剂，并可用作预防或治疗由异常TNF-α产生引起的各种疾病的药剂，例如可用于治疗可通过IL-10治愈的慢性炎症性疾病、急性炎症性疾病、感染引起的炎症性疾病、自身免疫疾病、过敏性疾病和TNF-α介导的疾病。
• THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
  申请人：Nakagawa Haruto

  公开号：US20100179157A1

  公开（公告）日：2010-07-15

  The present invention provides a novel therapeutic drug for cerebral infarction, which contains a piperazine compound as an active ingredient. The compound of the present invention can be provided as a novel therapeutic drug for cerebral infarction having an effect of suppressing brain injury volume or improving neurological deficit, since it suppresses production of plural inflammatory cytokines and chemokines present in the brain such as TNF-α, IL-1β, IL-6 and MCP-1 and the like.

  本发明提供了一种新型治疗脑梗死的药物，其包含一种哌嗪化合物作为活性成分。本发明的化合物可以作为一种新型治疗脑梗死的药物，具有抑制脑损伤体积或改善神经功能缺陷的作用，因为它抑制了存在于脑内的多种炎症细胞因子和趋化因子（如TNF-α、IL-1β、IL-6和MCP-1等）的产生。
• PIPERAZINE COMPOUNDS AND MEDICINAL USE THEREOF
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP1029851A1

  公开（公告）日：2000-08-23

  Piperazine compounds represented by the following general formula (I) or pharmaceutically acceptable salts thereof and drugs comprising these compounds, wherein R1 and R2 represent each hydrogen, halogeno, lower alkyl, lower alkoxy, optionally substituted amino, nitro, hydroxy or cyano; R3, R4 and R5 represent each hydrogen, halogeno, lower alkyl, lower alkoxy, nitro, optionally substituted amino or hydroxy; R6 and R7 represent each hydrogen, optionally halogenated lower alkyl, aralkyl, acyl or halogenated lower acyl; R8 and R9 represent each hydrogen or lower alkyl; Y represents lower alkylene, etc.; and the ring A represents phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl. Because of having excellent TNF-α production inhibitory effect and/or IL-10 production promoting effect, these compounds are useful as TNF-α production inhibitors and/or IL-10 production promoters with high safety. They are useful as preventives or remedies for, e.g., chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases caused by infection, autoimmune diseases, allergic diseases and other TNF-α-mediated diseases.

  由以下通式(I)代表的哌嗪化合物或其药学上可接受的盐以及包含这些化合物的药物，其中 R1 和 R2 分别代表氢、卤素、低级烷基、低级烷氧基、任选取代的氨基、硝基、羟基或氰基；R3、R4 和 R5 分别代表氢、卤素、低级烷基、低级烷氧基、硝基、任选取代的氨基或羟基； R6 和 R7 分别代表氢、任选卤代低级烷基、芳基、酰基或卤代低级酰基； R8 和 R9 分别代表氢或低级烷基； Y 代表低级亚烷基等。环 A 代表苯基、嘧啶基、噻唑基、吡啶基、吡嗪基或咪唑基。由于这些化合物具有优异的 TNF-α 生成抑制作用和/或 IL-10 生成促进作用，因此可用作 TNF-α 生成抑制剂和/或 IL-10 生成促进剂，安全性高。它们可用于预防或治疗慢性炎症性疾病、急性炎症性疾病、感染引起的炎症性疾病、自身免疫性疾病、过敏性疾病和其他TNF-α介导的疾病。
• THERAPEUTIC AGENT FOR NONVIRAL HEPATITIS
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1757593A1

  公开（公告）日：2007-02-28

  The present invention provides a therapeutic drug for non-viral hepatitis, which contains a piperazine compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明提供了一种治疗非病毒性肝炎的药物，它含有由下式（I）代表的哌嗪化合物 或其药学上可接受的盐作为活性成分。
• Therapeutic agent for cerebral infarction
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP2532658A1

  公开（公告）日：2012-12-12

  The present invention provides a novel therapeutic drug for cerebral infarction, which contains a piperazine compound as an active ingredient. The compound of the present invention can be provided as a novel therapeutic drug for cerebral infarction having an effect of suppressing brain injury volume or improving neurological deficit, since it suppresses production of plural inflammatory cytokines and chemokines present in the brain such as TNF-α, IL-1β, IL-6 and MCP-1 and the like.

  本发明提供了一种新型脑梗塞治疗药物，其有效成分为哌嗪化合物。 本发明的化合物可以作为一种新型脑梗塞治疗药物，具有抑制脑损伤体积或改善神经功能缺损的作用，因为它可以抑制脑内存在的多种炎性细胞因子和趋化因子，如 TNF-α、IL-1β、IL-6 和 MCP-1 等的产生。