1-[4,4-bis(4-fluorophenyl)butyl]-4-(2-methoxy-3-phenylaminopropyl)piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[4,4-bis(4-fluorophenyl)butyl]-4-(2-methoxy-3-phenylaminopropyl)piperazine
• 英文别名: N-[3-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]-2-methoxypropyl]aniline
• 化学式: C₃₀H₃₇F₂N₃O
• 分子量: 493.64
• InChiKey: AKDRTSVLFIAYML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  27.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-[4,4-双(4-氟苯基)丁基]哌嗪 在 盐酸 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-[4,4-bis(4-fluorophenyl)butyl]-4-(2-methoxy-3-phenylaminopropyl)piperazine
  参考文献：
  名称：

  Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities

  摘要：

  Two types of novel diphenylalkyl piperazine derivatives containing the thio or aminopropanol moiety substituted by phenyl or benzyl group were synthesized, and evaluated for their calcium antagonistic and antioxidative activities. These compounds showed apparent inhibitions against KCl-induced contractions in isolated rat aorta. Among them, phenylamino compound 9 and benzylamino compound 13 also possessed potent inhibitory activities against auto-oxidative lipid peroxidations in canine brain homogenates. Two representative compounds 3a and 9 were evaluated for their inhibitory activities against KCl-induced contractions in isolated canine arteries (basilar, coronary, mesenteric, and renal). Both compounds showed the most potent inhibitions to basilar artery. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00322-0

文献信息

• Novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter
  作者：Makoto Kimura、Tomoko Masuda、Koji Yamada、Masaki Mitani、Nobuo Kubota、Nobuyuki Kawakatsu、Kenichi Kishii、Masato Inazu、Yuji Kiuchi、Katsuji Oguchi、Takayuki Namiki

  DOI：10.1016/s0968-0896(03)00428-0

  日期：2003.9

  The novel diphenyl piperazine derivatives containing the phenyl substituted aminopropanol moiety, including 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1, which were modified at the connective between the diphenyl and piperazine moieties, have been found to be potent dopamine uptake inhibitors. To study the further structure-activity relationship (SAR) of these compounds

  含有苯基取代的氨基丙醇部分的新型二苯基哌嗪衍生物，包括1- [4,4-双（4-氟苯基）丁基] -4- [2-羟基-3-（苯基氨基）丙基]哌嗪1，在已经发现二苯基和哌嗪部分之间的连接是强力的多巴胺摄取抑制剂。为了研究这些化合物的进一步的构效关系（SAR），合成了一个新的系列，并对1的2-羟基-3-苯基氨基丙基部分进行了修饰。该系列的多巴胺转运蛋白（DAT）结合亲和力为[大鼠纹状体膜中的3H] GBR12935。大多数化合物显示出中等至高的DAT结合亲和力，有些化合物的活性与多巴胺摄取抑制剂的化合物1或GBR12909相当，IC（50）值为纳摩尔范围。SAR建议，在与DAT进行有效相互作用时，可能会在1的苯氨基部分的苯环周围存在空间限制，仅允许小尺寸的取代基，但在4位的碱性部分除外。另外，在1的3-氨基-2-丙醇部分的SAR表明，具有电子给体取代基的氮原子或未取代的氮原子以及羟基对于激发有效的DAT结合亲合力是理想的。
• DOPAMINE REINCORPORATION INHIBITOR
  申请人：POLA CHEMICAL INDUSTRIES, INC.

  公开号：EP0706796A1

  公开（公告）日：1996-04-17

  A dopamine (DA) reincorporation inhibitor containing a compound represented by general formula (1) or a physiologically acceptable salt thereof as the active ingredient, wherein R¹ and R² represent each hydrogen or halogen; R³ represents hydrogen, alkyl or acyl; R⁴ represents hydrogen, alkyl, acyl, alkylsulfonyl or optionally esterified carboxyl; Ar represents optionally substituted phenyl or a nitrogenous monocyclic heteroaromatic group; m represents a number of 1 to 5; and n represents a number of 0 to 5. This inhibitor does not produce any side effect, is safe, has potent activities of inhibiting DA reincorporation and enhancing autonomic movement, and is very useful for treating Parkinson's syndrome believed to be a disease caused by DA deficiency.

  一种含有通式(1)代表的化合物或其生理上可接受的盐作为活性成分的多巴胺（DA）再钙化抑制剂，其中R¹和R²分别代表氢或卤素；R³代表氢、烷基或酰基；R⁴代表氢、烷基、酰基、烷基磺酰基或任选酯化的羧基；Ar代表任选取代的苯基或含氮单环杂芳基；m代表1至5的数字；n代表0至5的数字。这种抑制剂不会产生任何副作用，安全可靠，具有抑制 DA 重归并和增强自律神经运动的强效活性，对治疗帕金森综合症（据认为是一种由 DA 缺乏引起的疾病）非常有用。
• DOPAMINE RE-UPTAKE INHIBITORS FOR THE TREATMENT OF PARKINSON'S SYNDROME
  申请人：POLA CHEMICAL INDUSTRIES, INC.

  公开号：EP0706796B1

  公开（公告）日：2001-02-28
• US5747493A
  申请人：——

  公开号：US5747493A

  公开（公告）日：1998-05-05
• Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities
  作者：Makoto Kimura、Tomoko Masuda、Koji Yamada、Nobuo Kubota、Nobuyuki Kawakatsu、Masaki Mitani、Kenichi Kishii、Masato Inazu、Takayuki Namiki

  DOI：10.1016/s0960-894x(02)00322-0

  日期：2002.8

  Two types of novel diphenylalkyl piperazine derivatives containing the thio or aminopropanol moiety substituted by phenyl or benzyl group were synthesized, and evaluated for their calcium antagonistic and antioxidative activities. These compounds showed apparent inhibitions against KCl-induced contractions in isolated rat aorta. Among them, phenylamino compound 9 and benzylamino compound 13 also possessed potent inhibitory activities against auto-oxidative lipid peroxidations in canine brain homogenates. Two representative compounds 3a and 9 were evaluated for their inhibitory activities against KCl-induced contractions in isolated canine arteries (basilar, coronary, mesenteric, and renal). Both compounds showed the most potent inhibitions to basilar artery. (C) 2002 Elsevier Science Ltd. All rights reserved.