4-amino-1-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butane | 854411-89-5

• 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: 4-amino-1-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butane
• 英文别名: 4-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butan-1-amine；4-[4-(3-chloro-2-methoxyphenyl)piperazin-1-yl]butyl-1-amine；4-[4-(3-chloro-2-methoxyphenyl)piperazin-1-yl]butylamine；4-(4-(3-chloro-2-methoxyphenyl)-piperazin-1-yl)-butylamine；4-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butylamine；1-Piperazinebutanamine, 4-(3-chloro-2-methoxyphenyl)-；4-[4-(3-chloro-2-methoxyphenyl)piperazin-1-yl]butan-1-amine
• CAS: 854411-89-5
• 化学式: C₁₅H₂₄ClN₃O
• 分子量: 297.828
• InChiKey: AXQNYRWWPAVLSM-UHFFFAOYSA-N

物化性质

• 沸点：
  441.4±45.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-1-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butane 、 [2.2]paracyclophane-4-carboxylic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以91%的产率得到Tricyclo[8.2.2.2^4,7]hexadeca-1(13),4,6,10(14),11,15-hexaene-5-carboxylic acid {4-[4-(3-chloro-2-methoxy-phenyl)-piperazin-1-yl]-butyl}-amide
  参考文献：
  名称：

  花式生物等排体：作为超亲和性多巴胺D3受体拮抗剂的新型对环烷衍生物。

  摘要：

  对化学多样性空间的探索取决于新型生物等位元素的发现。作为我们对双层芳烃替代物的研究的延续，我们在此报告4和6型[2.2]对环烷衍生的多巴胺D3受体拮抗剂。对于最有希望的带有2-甲氧基苯基取代基的测试化合物6a，采用立体控制的制备方法当对映异构体（R）-6a（FAUC 418）和（S）-6a的平面手性引起D3结合的显着差异时，可以通过K（i）分别为0.19和3.0 nM的值进行分析。功能实验表明，D3对6型对环烷衍生物具有拮抗作用。为阐明推定的生物活性低能构象，进行了基于DFT的研究，包括诊断性磁屏蔽性质的计算。

  DOI：

  10.1021/jm060138d
• 作为产物：
  描述：

  1-(3-chloro-2-methoxyphenyl)piperazine 在 potassium carbonate 、 肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 3.0h， 生成 4-amino-1-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butane
  参考文献：
  名称：

  High Affinity Dopamine D₃ Receptor (D₃R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D₃R Knockout Mice

  摘要：

  The dopamine D-3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (K-i = 0.12 nM) and 32 (K-i = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing selfadministration of heroin in wild-type but not D3R knockout mice.

  DOI：

  10.1021/acs.jmedchem.5b00776

文献信息

• A Series of 18F-Labelled Pyridinylphenyl Amides as Subtype-Selective Radioligands for the Dopamine D3 Receptor
  作者：Carsten Hocke、Simone Maschauer、Harald Hübner、Stefan Löber、Wolfgang Utz、Torsten Kuwert、Peter Gmeiner、Olaf Prante

  DOI：10.1002/cmdc.201000067

  日期：2010.6.7

  Synthesis, biological activity, and structure–selectivity relationship (SSR) studies of a novel series of potential dopamine D3 receptor radioligands as imaging agents for positron emission tomography (PET) are reported. Considering a structurally diverse library of D3 ligands, SSR studies were performed for a new series of fluorinated pyridinylphenyl amides using CoMFA and CoMSIA methods. The in vitro

  报道了一系列新型的潜在多巴胺D3受体放射性配体作为正电子发射断层显像（PET）的成像剂的合成，生物活性和结构-选择性关系（SSR）研究。考虑到D3配体在结构上的多样性，使用CoMFA和CoMSIA方法对一系列新的氟化吡啶基苯基酰胺进行了SSR研究。预测的联苯酰胺配体系列9 a – d的体外D3亲和力显示单位数到亚纳摩尔效价（ K i = 0.52–1.6 n M），与110-210的D2亚型相比，具有出色的D3选择性。测试化合物9 a – c的倍数。通过18 F亲核取代Br或NO 2进行的放射性氟化导致[ 18 F] 9 a – d的放射化学产率为66–92％。但是，[ 18 F] 9 b和[ 18 F] 9 d的比活不够，因此无法用于体内研究。[ 18 F] 9 a和[ 18 F] 9 c的生物分布研究使用大鼠脑部放射自显影技术揭示了心室中的蓄积，因此表明[ 18 F] 9 a和[ 18
• [DE] CARBOXAMIDE DES INDOLIZINS UND SEINER AZA- UND DIAZADERIVATE<br/>[EN] INDOLIZINE CARBOXAMIDES AND THE AZA AND DIAZA DERIVATIVES THEREOF<br/>[FR] CARBOXAMIDES D'INDOLIZINE ET LEURS AZA- ET DIAZA-DERIVES
  申请人：SANOL ARZNEI SCHWARZ GMBH

  公开号：WO2006015737A1

  公开（公告）日：2006-02-16

  Die vorliegende Erfindung betrifft neurorezeptoraktive Carboxamid-substituierte Indolizin­-Derivate der allgemeinen Formel (I) wobei X eine Gruppe mit der allgemeinen Formel (X1) repräsentiert.

  本发明涉及具有神经受体活性的羧酰胺取代的吲哩啉衍生物，其一般式为（I），其中X代表一种具有一般式（X1）的基团。
• Indolizine Carboxamides and Aza and Diaza Derivatives Thereof
  申请人：Gmeiner Peter

  公开号：US20080051409A1

  公开（公告）日：2008-02-28

  The present invention concerns neuroreceptor-active carboxamide-substituted indolizine derivatives of general formula I wherein X represents a group of general formula X1

  本发明涉及一般式I的神经受体活性羧酰胺取代吲哚啉衍生物，其中X代表一般式X1的基团。
• Azaindole Carboxamides
  申请人：Gmeiner Peter

  公开号：US20070299091A1

  公开（公告）日：2007-12-27

  The invention relates to azaindole derivatives of general formula (I), wherein X represents a group of general formula (X1). Said compounds have a therapeutic potential in the treatment of diseases that are accompanied by an impaired dopamine metabolism and/or abnormal serotonin-5-HT1a signal transmission.

  本发明涉及通式(I)的吡唑吲衍生物，其中X代表通式（X1）的一个基团。所述化合物在治疗伴随有受损的多巴胺代谢和/或异常的5-羟色胺-1a信号传递的疾病方面具有治疗潜力。
• Synthesis and evaluation of fluoro substituted pyridinylcarboxamides and their phenylazo analogues for potential dopamine D3 receptor PET imaging
  作者：Natascha Nebel、Simone Maschauer、Amelie L. Bartuschat、Stefanie K. Fehler、Harald Hübner、Peter Gmeiner、Torsten Kuwert、Markus R. Heinrich、Olaf Prante、Carsten Hocke

  DOI：10.1016/j.bmcl.2014.10.043

  日期：2014.12

  A series of fluoro substituted pyridinylcarboxamides and their phenylazo analogues with high affinity and selectivity for the dopamine D3 receptor was synthesized by the use of 6-fluoropyridine-3-carbonyl chloride (1) and fluorophenylazocarboxylic ester (2). Several of these compounds (9a-e and 10a-h) have been evaluated in vitro, among which 9b, 10a, 10c and 10d proved to have at least single-digit nanomolar affinity for D3. They also exhibit considerable selectivity over the other dopamine receptor subtypes and noteworthy selectivity over the structurally related serotonin receptor subtypes 5-HT1A and 5-HT2, offering potential radiotracers for positron emission tomography. (C) 2014 Elsevier Ltd. All rights reserved.