1-(3-chlorophenyl)-4-ethylpiperazine | 141510-94-3

• 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-(3-chlorophenyl)-4-ethylpiperazine
• 英文别名: 1-(3-Chloro-phenyl)-4-ethyl-piperazine
• CAS: 141510-94-3
• 化学式: C₁₂H₁₇ClN₂
• 分子量: 224.733
• InChiKey: OZSJNFWCZQEKCI-UHFFFAOYSA-N

物化性质

• 沸点：
  330.0±37.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 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：
  2

反应信息

• 作为反应物：
  描述：

  碘乙烷 、 1-(3-chlorophenyl)-4-ethylpiperazine 在 铜 作用下， 以 四氢呋喃 为溶剂， 以48%的产率得到4-(3-chlorophenyl)-1,1-diethylpiperazin-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 、 1-氯-3-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83%的产率得到1-(3-chlorophenyl)-4-ethylpiperazine
  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] TRIAZACYCLODODECANSULFONAMIDE ("TCD")-BASED PROTEIN SECRETION INHIBITORS<br/>[FR] INHIBITEURS DE SÉCRÉTION DE PROTÉINE À BASE DE TRIAZACYCLODODÉCANSULFONAMIDE ("TCD")
  申请人：KEZAR LIFE SCIENCES

  公开号：WO2019178510A1

  公开（公告）日：2019-09-19

  Provided herein are triazacyclododecansulfonamide ("TCD")-based protein secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I) and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.

  本文提供了基于三氮杂环十二烷磺酰胺（"TCD"）的蛋白质分泌抑制剂，例如Sec61的抑制剂，其制备方法，相关的药物组合物，以及使用它们的方法。例如，本文提供了符合Formula（I）的化合物及其药用盐和包括它们的组合物。本文披露的化合物可以用于治疗炎症和/或癌症等疾病。
• [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 central nervous system (CNS) agents. 5. Effect of the hydrocarbon chain on the affinity of 4-substituted 1-(3-chlorophenyl)piperazines for 5-HT1A receptor sites
  作者：Jerzy L. Mokrosz、Marzena Pietrasiewicz、Beata Duszynska、Marek T. Cegla

  DOI：10.1021/jm00091a004

  日期：1992.6

  contribute to their 5-HT1A affinity. The specific binding constant was defined as the receptor affinity of the protonated species of compounds under physiological conditions. The range of Ki(AH+) = 1 - 3 x 10(-11) M is a specific affinity limit of the investigated class of compounds at the 5-HT1A receptor sites.

  研究了模型4-取代的1-（3-氯苯基）哌嗪12-31的烃链对其对5-HT1A受体位点的亲和力的影响。发现4-正烷基链的延长强烈增加了所研究化合物的5-HT1A亲和力。正己基衍生物20的亲和力达到最大值（Ki ＝ 2.67nM）。已表明1-芳基哌嗪的N-4取代基的疏水相互作用显着地促进了它们的5-HT1A亲和力。特异性结合常数定义为在生理条件下化合物的质子化物质的受体亲和力。Ki（AH +）的范围为1-3 x 10（-11）M是在5-HT1A受体位点上所研究化合物类别的特定亲和力极限。
• 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。