1-ethyl-4-(3-(trifluoromethyl)phenyl)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-(trifluoromethyl)phenyl)piperazine
• 英文别名: 1-Ethyl-4-[3-(trifluoromethyl)phenyl]piperazine
• 化学式: C₁₃H₁₇F₃N₂
• 分子量: 258.287
• InChiKey: YPKLXEHKFHQREX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  碘乙烷 、 1-ethyl-4-(3-(trifluoromethyl)phenyl)piperazine 在 铜 作用下， 以 四氢呋喃 为溶剂， 以21%的产率得到1,1-diethyl-4-(3-(trifluoromethyl)phenyl)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 、 间溴三氟甲苯 在 potassium phosphate 、 copper(l) iodide 、 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 以64%的产率得到1-ethyl-4-(3-(trifluoromethyl)phenyl)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。
• Structure-Activity Relationship Studies of CNS Agents, XIX: Quantitative Analysis of the Alkyl Chain Effects on the 5-HT1A and 5-HT2 Receptor Affinities of 4-Alkyl-1-arylpiperazines and Their Analogs
  作者：Jerzy L. Mokrosz、Maria J. Mokrosz、Sijka Charakchieva-Minol、Maria H. Paluchowska、Andrzej J. Bojarski、Beata Duszyńska

  DOI：10.1002/ardp.19953280210

  日期：——

  The 5‐HT1a and 5‐HT2 receptor affinity of a set of 44 N‐alkylated 1‐arylpiperazines and their analogs has been analyzed: the n‐hexyl derivatives were the most potent and the most selective 5‐HT1a ligands of all the investigated N‐alkyl homologues. The alkyl chain may stablize the 5‐HT1a receptor‐ligand complex by hydrophobic forces. A set of the alkyl substituent contributions (Cht1a) for prediction

  已经分析了一组 44 N-烷基化 1-芳基哌嗪及其类似物的 5-HT1a 和 5-HT2 受体亲和力：在所有研究的 N 中，正己基衍生物是最有效和最具选择性的 5-HT1a 配体烷基同系物。烷基链可以通过疏水力稳定 5-HT1a 受体-配体复合物。在 Free-Wilson 分析的基础上，已经定义了一组用于预测 1-芳基哌嗪和相关化合物的 N-烷基衍生物的 5-HT1a 亲和力的烷基取代贡献 (Cht1a)。
• TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
  申请人：Tao Chunlin

  公开号：US20080176853A1

  公开（公告）日：2008-07-24

  The invention provides for Triazine derivatives and their use to modulate protein kinase activity in a variety of conditions and diseases.

  本发明提供了三嗪衍生物及其在多种疾病和情况下调节蛋白激酶活性的用途。
• STYRYL-TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
  申请人：Tao Chunlin

  公开号：US20120178758A1

  公开（公告）日：2012-07-12

  The invention provides Styryl-Triazine derivatives, and further provides methods of using these compounds to modulate protein kinases and to treat protein kinase mediated diseases.

  本发明提供了Styryl-Triazine衍生物，并进一步提供了使用这些化合物调节蛋白激酶和治疗蛋白激酶介导疾病的方法。
• UREIDOPHENYL SUBSTITUTED TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
  申请人：Tao Chunlin

  公开号：US20120202818A1

  公开（公告）日：2012-08-09

  The present invention provides Uredophenyl substituted triazine derivatives and provides methods of using these compounds to modulate protein kinases and methods of using these compounds to treat protein kinase mediated diseases and conditions.

  本发明提供了Uredophenyl取代的三嗪衍生物，并提供了使用这些化合物调节蛋白激酶和使用这些化合物治疗蛋白激酶介导的疾病和病症的方法。