(-)-2(R)-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[(4-piperidinyl-amino) acetyl]piperazine | 522607-93-8

• 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: (-)-2(R)-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[(4-piperidinyl-amino) acetyl]piperazine
• 英文别名: 1-[(R)-2-(3,4-Dichloro-phenyl)-4-(3,5-dimethyl-benzoyl)-piperazin-1-yl]-2-(piperidin-4-ylamino)-ethanone；1-[(2R)-2-(3,4-dichlorophenyl)-4-(3,5-dimethylbenzoyl)piperazin-1-yl]-2-(piperidin-4-ylamino)ethanone
• CAS: 522607-93-8
• 化学式: C₂₆H₃₂Cl₂N₄O₂
• 分子量: 503.472
• InChiKey: MNUMOFSSNQUTGL-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-2(R)-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[(4-piperidinyl-amino) acetyl]piperazine 在 盐酸 、 乙胺嗪 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S)-2-amino-1-[4-[[2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,5-dimethylbenzoyl)piperazin-1-yl]-2-oxoethyl]amino]piperidin-1-yl]-3-(4-hydroxyphenyl)propan-1-one
  参考文献：
  名称：

  Synthesis and NK1/NK2 binding activities of a series of diacyl-substituted 2-arylpiperazines

  摘要：

  The synthesis and binding affinity for hNK(1) and hNK(2) receptors of a series of diacyl substituted 2-aryl piperazines are described. SAR evaluation led to the racemic derivative 11g as an apparent dual inhibitor. Chiral chromatographic separation of 11g led to the observation that NK1 activity was shown by one enantiomer (13a) and NK2 activity was shown by the other enantiomer (13b). X-ray crystallographic analysis of the crystalline di-BOC derivative of the NK2, active piperazine (15) showed that the 2R configuration was associated with NK2 activity. Further derivatization indicated that dual NK1/NK2 activity could be built into the 2R series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00645-5
• 作为产物：
  描述：

  3,5-二甲基苯甲酸 在 盐酸 、 乙胺嗪 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (-)-2(R)-(3,4-Dichlorophenyl)-4-[3,5-dimethylbenzoyl]-1-[(4-piperidinyl-amino) acetyl]piperazine
  参考文献：
  名称：

  Synthesis and NK1/NK2 binding activities of a series of diacyl-substituted 2-arylpiperazines

  摘要：

  The synthesis and binding affinity for hNK(1) and hNK(2) receptors of a series of diacyl substituted 2-aryl piperazines are described. SAR evaluation led to the racemic derivative 11g as an apparent dual inhibitor. Chiral chromatographic separation of 11g led to the observation that NK1 activity was shown by one enantiomer (13a) and NK2 activity was shown by the other enantiomer (13b). X-ray crystallographic analysis of the crystalline di-BOC derivative of the NK2, active piperazine (15) showed that the 2R configuration was associated with NK2 activity. Further derivatization indicated that dual NK1/NK2 activity could be built into the 2R series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00645-5

文献信息

• Combination treatment for depression and anxiety
  申请人：Pfizer Inc.

  公开号：US20040006135A1

  公开（公告）日：2004-01-08

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g., a substance P receptor antagonist) in combination with an NK-3 antagonist agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and an NK-3 antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）的抑郁症或焦虑症的方法，该方法通过给哺乳动物（包括人类）注射一种中枢神经系统渗透的NK-1受体拮抗剂（例如物质P受体拮抗剂）与NK-3拮抗剂药物的组合来实现。本发明还涉及含有药学上可接受载体、中枢神经系统渗透的NK-1受体拮抗剂和NK-3拮抗剂的药物组合物。
• Combination, for treating depression and anxiety, containing an NK-3 receptor antagonist and a CNS penetrant NK-1 receptor antagonist
  申请人：Pfizer Products Inc.

  公开号：EP1192952A2

  公开（公告）日：2002-04-03

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g. a substance P receptor antagonist) in combination with an NK-3 antagonist agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and an NK-3 antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）抑郁症或焦虑症的方法，其方法是向哺乳动物施用中枢神经系统穿透性NK-1受体拮抗剂（例如P物质受体拮抗剂）与NK-3拮抗剂联合制剂。它还涉及含有药学上可接受的载体、中枢神经系统穿透性 NK-1 受体拮抗剂和 NK-3 拮抗剂的药物组合物。
• PIPERAZINO DERIVATIVES AS NEUROKININ ANTAGONISTS
  申请人：SCHERING CORPORATION

  公开号：EP0937069B1

  公开（公告）日：2006-05-03
• COMBINATION TREATMENT FOR DEPRESSION AND ANXIETY BY NK1 AND NK3 ANTAGONISTS
  申请人：Pfizer Products Inc.

  公开号：EP1517708A1

  公开（公告）日：2005-03-30
• US5968929A
  申请人：——

  公开号：US5968929A

  公开（公告）日：1999-10-19