1-(6-phenylpyridin-2-yl)piperazine | 331767-58-9

• 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-phenylpyridin-2-yl)piperazine
• 英文别名: 1-(6-Phenyl-pyridin-2-yl)-piperazine
• CAS: 331767-58-9
• 化学式: C₁₅H₁₇N₃
• 分子量: 239.32
• InChiKey: UBDNRDRCJUAJNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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-phenylpyridin-2-yl)piperazine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 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 9.0h， 生成
  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：

  4-BOC-1-(6-溴-2-吡啶基)哌嗪 在 potassium tert-butylate 、 palladium diacetate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-(6-phenylpyridin-2-yl)piperazine
  参考文献：
  名称：

  SYA16263结构亲和关系研究；D2 受体相互作用对于抑制阿朴吗啡诱导的小鼠攀爬行为是必不可少的吗？

  摘要：

  多巴胺 (DA) 和血清素 (5-HT) 受体是开发抗精神病药的主要目标。每种受体亚型对抗精神病药物药理作用的具体作用仍不清楚。了解抗精神病药物与其在 DA 和 5-HT 受体亚型上的结合亲和力之间的关系对于抗精神病药物的发现非常重要，并可能导致新药的疗效增强。我们之前已经公开了 SYA16263 ( 5 ) 作为一种有趣的化合物，它对 D 2和 D 3受体具有中等放射性配体结合亲和力（分别为Ki  = 124 nM 和 86 nM），并且对 D 4和 5-HT 1A受体具有高结合亲和力（Ki = 3.5 nM 和 1.1 nM）。此外，我们已经证明 SYA16263 ( 5 ) 具有功能选择性并产生类似抗精神病药的行为，但不会在小鼠中诱发僵住症。基于其药理学特征，我们选择SYA16263 ( 5 ) 来研究其结构-亲和力关系，以期获得具有受体亚型选择性的新类似物。在这项研究中，我们介绍了结构修饰的

  DOI：

  10.1016/j.bmc.2020.115943

文献信息

• Substituted piperazine derivatives, the preparation thereof and their use as medicaments
  申请人：Boehringer Ingelheim Pharm GmbH & Co, KG

  公开号：US06818644B1

  公开（公告）日：2004-11-16

  The present invention relates to substituted piperazine derivatives of general formula wherein Ra, Rb, Rc Rf, Rg and m, n and X are defined as in claim 1, the isomers and salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyseride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.

  本发明涉及一般式的取代哌嗪衍生物，其中Ra、Rb、Rc、Rf、Rg和m、n和X的定义如权利要求书中所述，其异构体和盐，特别是其生理上可接受的盐，这些盐是微粒体三酰甘油转移蛋白（MTP）的有价值的抑制剂，包含这些化合物的药物以及它们的用途，以及其制备。
• SUBSTITUIERTE PIPERAZINDERIVATE, IHRE HERSTELLUNG UND IHRE VERWENDUNG ALS INHIBITOREN DES MIKROSOMALEN TRIGLYZERID-TRANSFERPROTEINS (MTP)
  申请人：Boehringer Ingelheim Pharma KG

  公开号：EP1228053A1

  公开（公告）日：2002-08-07
• US6818644B1
  申请人：——

  公开号：US6818644B1

  公开（公告）日：2004-11-16
• [DE] SUBSTITUIERTE PIPERAZINDERIVATE, IHRE HERSTELLUNG UND IHRE VERWENDUNG ALS INHIBITOREN DES MIKROSOMALEN TRIGLYZERID-TRANSFERPROTEINS (MTP)<br/>[EN] SUBSTITUTED PIPERAZINE DERIVATIVES, THE PRODUCTION AND USE THEREOF AS INHIBITORS OF THE MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN (MTP)<br/>[FR] DERIVES DE PIPERAZINE SUBSTITUES, FABRICATION ET UTILISATION EN TANT QU'AGENTS PHARMACEUTIQUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2001021604A1

  公开（公告）日：2001-03-29

  Die vorliegende Erfindung betrifft substituierte Piperazinderivate der allgemeinen Formel (I), in der n die Zahl 1, 2, 3, 4 oder 5, m die Zahl 2 oder 3, X eine Kohlenstoff-Kohlenstoff-Bindung, ein Sauerstoffatom, eine Methylen-, Ethylen-, Imino- oder N-(C1-3-Alkyl)- iminogruppe, Ra eine substituierte Phenylgruppe oder Heteroarylgruppe, Rb und Rc unabhängig voneinander ein Wasserstoffatom oder eine C1-3-Alkylgruppe und Rf und Rg, die gleich oder verschieden sein können, Wasserstoffatom, C1-6-Alkylgruppen, C3-7-Cycloalkylgruppen, Phenyl, Heteroaryl, Phenyl-C1-3-alkyl-oder Heteroaryl-C1-3-alkylgruppen, Rf und Rg zusammen mit dem dazwischenliegenden Stickstoffatem eine 3- bis 7-gliedrige Cycloalkyleniminogruppe, wobei die Methylengruppe in Position 4 in eine 6- oder 7-gliedrigen Cycloalkenyleniminogruppe zusätzlich durch ein Sauerstoff- oder Schwefelatom, durch eine Sulfinyl-, Sulfonyl-, Imino- oder-(C1-3-Alkyl)-iminogruppe ersetzt sein kann, bedeutet, deren Isomere und deren Salze, insbesondere deren physiologisch verträgliche Salze, welche wertvolle Inhibitoren des mikrosomalen Triglyzerid- Transferproteins (MTP) darstellen, diese Verbidungen enthaltende Arzneimittel und deren Verwendung sowie deren Herstellung.
• <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.