1-ethyl-4-(3-fluorophenyl)piperazine

• 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: 1-ethyl-4-(3-fluorophenyl)piperazine
• 化学式: C₁₂H₁₇FN₂
• 分子量: 208.279
• InChiKey: LGSYGIREHIKOBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-ethyl-4-(3-fluorophenyl)piperazine 、 碘乙烷 在 铜 作用下， 以 四氢呋喃 为溶剂， 以64%的产率得到1,1-diethyl-4-(3-fluorophenyl)piperazin-1-ium iodide
  参考文献：
  名称：

  Dissection of N,N-diethyl-N′-phenylpiperazines as α7 nicotinic receptor silent agonists

  摘要：

  The alpha 7 nicotinic acetylcholine receptor (nAChR) is a target for control of inflammation-related phenomena via compounds that are able to selectively induce desensitized states of the receptor. Compounds that selectively desensitize, without facilitating significant channel activation, are termed 'silent agonists' because they can be discriminated from antagonists by the currents evoked with co-application with type II positive allosteric modulators (PAMs). One example is N, N-diethyl-N'-phenyl-piperazine(diEPP) (J. Pharm. Exp. Ther. 2014, 350, 665). We used Ullmann-type aryl amination to synthesize a panel of 27 compounds related to diEPP by substitutions at the aryl ring and in the linkage between the piperazine and phenyl rings. Two-electrode voltage clamping of the human a7 nAChR expressed in Xenopus oocytes revealed that it was possible to tune the behavior of compounds to show enhanced desensitization without corresponding partial agonist activity such that trifluoromethyl and carboxamide aryl substituents showed 33 to 46-fold larger PAM-dependent net-charge responses, indicating selective partitioning of the ligand receptor complexes into the desensitized state. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.017
• 作为产物：
  描述：

  N-乙基哌嗪 、 间氟碘苯 在 copper(l) iodide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 以75%的产率得到1-ethyl-4-(3-fluorophenyl)piperazine
  参考文献：
  名称：

  Dissection of N,N-diethyl-N′-phenylpiperazines as α7 nicotinic receptor silent agonists

  摘要：

  The alpha 7 nicotinic acetylcholine receptor (nAChR) is a target for control of inflammation-related phenomena via compounds that are able to selectively induce desensitized states of the receptor. Compounds that selectively desensitize, without facilitating significant channel activation, are termed 'silent agonists' because they can be discriminated from antagonists by the currents evoked with co-application with type II positive allosteric modulators (PAMs). One example is N, N-diethyl-N'-phenyl-piperazine(diEPP) (J. Pharm. Exp. Ther. 2014, 350, 665). We used Ullmann-type aryl amination to synthesize a panel of 27 compounds related to diEPP by substitutions at the aryl ring and in the linkage between the piperazine and phenyl rings. Two-electrode voltage clamping of the human a7 nAChR expressed in Xenopus oocytes revealed that it was possible to tune the behavior of compounds to show enhanced desensitization without corresponding partial agonist activity such that trifluoromethyl and carboxamide aryl substituents showed 33 to 46-fold larger PAM-dependent net-charge responses, indicating selective partitioning of the ligand receptor complexes into the desensitized state. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.017

文献信息

• [EN] NICOTINIC ACETYLCHOLINE RECEPTOR SILENT AGONISTS<br/>[FR] AGONISTES SILENCIEUX DU RÉCEPTEUR NICOTINIQUE D'ACÉTYLCHOLINE
  申请人：THE UNIV OF FLORIDA RES FOUND INC

  公开号：WO2017066558A1

  公开（公告）日：2017-04-20

  Derivatives of N,N-diethyl-N'- phenyl-piperazine, a silent agonist of the mammalian α7 nicotinic acetylcholine receptor, are provided. These silent agonists control the desensitization state of the receptor. Further provided are pharmaceutical compositions that allow the administration of the silent agonists of the disclosure to a subject animal or human in need of treatment for a pathological condition arising from such as inflammation. The novel silent agonists also may be co-administered to a patient simultaneously or consecutively with a type II positive allosteric modulator to modulate the activity of the receptor.

  N,N-二乙基-N'-苯基哌嗪的衍生物，作为哺乳动物α7尼古丁乙酰胆碱受体的沉默激动剂，已提供。这些沉默激动剂控制受体的耗散状态。还提供了允许将上述沉默激动剂给予需要治疗由炎症等病理状况引起的动物或人类的药物组合物。这种新型沉默激动剂也可以与II型正向变构调节剂同时或连续给予患者，以调节受体的活性。
• Nicotinic acetylcholine receptor silent agonists
  申请人：University of Florida Research Foundation, Inc.

  公开号：US10662191B2

  公开（公告）日：2020-05-26

  Derivatives of N,N-diethyl-N′-phenyl-piperazine, a silent agonist of the mammalian α7 nicotinic acetylcholine receptor, are provided. These silent agonists control the desensitization state of the receptor. Further provided are pharmaceutical compositions that allow the administration of the silent agonists of the disclosure to a subject animal or human in need of treatment for a pathological condition arising from such as inflammation. The novel silent agonists also may be co-administered to a patient simultaneously or consecutively with a type II positive allosteric modulator to modulate the activity of the receptor.

  本研究提供了哺乳动物 α7 尼古丁乙酰胆碱受体的沉默激动剂 N,N-二乙基-N′-苯基哌嗪的衍生物。这些沉默激动剂可控制受体的脱敏状态。此外，还提供了药物组合物，可将本公开的沉默激动剂施用给需要治疗炎症等病理状况的动物或人。新型沉默激动剂还可与 II 型正性异位调节剂同时或连续给患者用药，以调节受体的活性。
• 1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Chong Kun Dang Pharmaceutical Corp.

  公开号：EP3331864A2

  公开（公告）日：2018-06-13
• NICOTINIC ACETYLCHOLINE RECEPTOR SILENT AGONISTS
  申请人：THE UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.

  公开号：US20180298002A1

  公开（公告）日：2018-10-18

  Derivatives of N,N-diethyl-N′-phenyl-piperazine, a silent agonist of the mammalian α7 nicotinic acetylcholine receptor, are provided. These silent agonists control the desensitization state of the receptor. Further provided are pharmaceutical compositions that allow the administration of the silent agonists of the disclosure to a subject animal or human in need of treatment for a pathological condition arising from such as inflammation. The novel silent agonists also may be co-administered to a patient simultaneously or consecutively with a type II positive allosteric modulator to modulate the activity of the receptor.
• Dissection of N,N-diethyl-N′-phenylpiperazines as α7 nicotinic receptor silent agonists
  作者：Marta Quadri、Roger L. Papke、Nicole A. Horenstein

  DOI：10.1016/j.bmc.2015.12.017

  日期：2016.1

  The alpha 7 nicotinic acetylcholine receptor (nAChR) is a target for control of inflammation-related phenomena via compounds that are able to selectively induce desensitized states of the receptor. Compounds that selectively desensitize, without facilitating significant channel activation, are termed 'silent agonists' because they can be discriminated from antagonists by the currents evoked with co-application with type II positive allosteric modulators (PAMs). One example is N, N-diethyl-N'-phenyl-piperazine(diEPP) (J. Pharm. Exp. Ther. 2014, 350, 665). We used Ullmann-type aryl amination to synthesize a panel of 27 compounds related to diEPP by substitutions at the aryl ring and in the linkage between the piperazine and phenyl rings. Two-electrode voltage clamping of the human a7 nAChR expressed in Xenopus oocytes revealed that it was possible to tune the behavior of compounds to show enhanced desensitization without corresponding partial agonist activity such that trifluoromethyl and carboxamide aryl substituents showed 33 to 46-fold larger PAM-dependent net-charge responses, indicating selective partitioning of the ligand receptor complexes into the desensitized state. (C) 2015 Elsevier Ltd. All rights reserved.