1-(6-iodo-2-pyridyl)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-(6-iodo-2-pyridyl)piperazine
• 英文别名: 1-(6-iodopyridin-2-yl)piperazine；1-(6-Iodopyridin-2-yl)piperazine
• 化学式: C₉H₁₂IN₃
• 分子量: 289.119
• InChiKey: BAQQLHACDPXIPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-iodo-2-pyridyl)piperazine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 Nε-acryloyl-L-lysine-4-(6-iodopyridin-2-yl)piperazide*2TFA
  参考文献：
  名称：

  N^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling

  摘要：

  Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M-1 s(-1), which resulted in comprehensive structure activity relationships. Structure activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

  DOI：

  10.1021/acs.jmedchem.8b00286
• 作为产物：
  描述：

  1-(2-pyridyl)-4-tritylpiperazine 在 正丁基锂 、 N,N-二甲基乙醇胺 、 三氟乙酸 作用下， 以 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 1-(6-iodo-2-pyridyl)piperazine
  参考文献：
  名称：

  First selective lithiation of pyridylpiperazines: straightforward access to potent pharmacophores

  摘要：

  The three isomers of pyridylpiperazines have been lithiated for the first time. The use of a superbase, an aminoalkoxide containing lithiating agent overcomes the chelating influence of the basic piperazine nitrogens, so that selective mono lithiation occurred alpha to pyridine nitrogen. This methodology offers a new access to diverse potent pharmacophores not easily prepared by other routes. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.03.026

文献信息

• [EN] RADIOLABELED COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS RADIOMARQUÉS ET LEURS UTILISATIONS
  申请人：UNIV COLUMBIA

  公开号：WO2011140360A1

  公开（公告）日：2011-11-10

  The present invention relates to Radiolabeled Compounds labeled with fluorine, bromine, iodine, carbon, or tritium isotopes and methods of use thereof for treating or preventing a psychiatric disorder in a subject, for stabilizing the mood of a subject having a mood disorder, or as imaging agents for a serotonin receptor. Compositions comprising an imaging-effective amount of a Radiolabeled Compound are also disclosed.

  本发明涉及用氟、溴、碘、碳或氚同位素标记的放射性化合物，以及利用这些化合物治疗或预防受试者的精神障碍，稳定情绪障碍受试者的情绪，或作为血清素受体的成像剂的方法。还公开了包含成像有效量放射性标记化合物的组合物。
• RADIOLABELED COMPOUNDS AND USES THEREOF
  申请人：MANN Joseph John

  公开号：US20130156699A1

  公开（公告）日：2013-06-20

  The present invention relates to Radiolabeled Compounds labeled with fluorine, bromine, iodine, carbon, or tritium isotopes and methods of use thereof for treating or preventing a psychiatric disorder in a subject, for stabilizing the mood of a subject having a mood disorder, or as imaging agents for a serotonin receptor. Compositions comprising an imaging-effective amount of a Radiolabeled Compound are also disclosed.
• US9290463B2
  申请人：——

  公开号：US9290463B2

  公开（公告）日：2016-03-22
• <i>N</i>^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling
  作者：Robert Wodtke、Christoph Hauser、Gloria Ruiz-Gómez、Elisabeth Jäckel、David Bauer、Martin Lohse、Alan Wong、Johanna Pufe、Friedrich-Alexander Ludwig、Steffen Fischer、Sandra Hauser、Dieter Greif、M. Teresa Pisabarro、Jens Pietzsch、Markus Pietsch、Reik Löser

  DOI：10.1021/acs.jmedchem.8b00286

  日期：2018.5.24

  Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M-1 s(-1), which resulted in comprehensive structure activity relationships. Structure activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.
• First selective lithiation of pyridylpiperazines: straightforward access to potent pharmacophores
  作者：Frédéric Louërat、Philippe Gros、Yves Fort

  DOI：10.1016/j.tet.2005.03.026

  日期：2005.5

  The three isomers of pyridylpiperazines have been lithiated for the first time. The use of a superbase, an aminoalkoxide containing lithiating agent overcomes the chelating influence of the basic piperazine nitrogens, so that selective mono lithiation occurred alpha to pyridine nitrogen. This methodology offers a new access to diverse potent pharmacophores not easily prepared by other routes. (c) 2005 Elsevier Ltd. All rights reserved.