1-(3-chloro-2-methoxyphenyl)piperazine | 391882-60-3

• 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-chloro-2-methoxyphenyl)piperazine
• 英文别名: 3-chloro-2-methoxyphenylpiperazine；1-(3-chloro-2-methoxy-phenyl)-piperazine；N-(3-chloro-2-methoxyphenyl)-piperazine；4-(3-chloro-2-methoxyphenyl)piperazine
• CAS: 391882-60-3
• 化学式: C₁₁H₁₅ClN₂O
• 分子量: 226.706
• InChiKey: CWLHQCGNSQBNIP-UHFFFAOYSA-N

物化性质

• 沸点：
  374.0±42.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-氯邻茴香胺 、 二(2-氯乙基)胺盐酸盐 在 potassium carbonate 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 48.0h， 以56%的产率得到1-(3-chloro-2-methoxyphenyl)piperazine
  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

• [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
  申请人：Clark D. Jerry

  公开号：US20050043309A1

  公开（公告）日：2005-02-24

  This invention relates to compounds of the formula 1 wherein G, D, A, Z, Q, X, Y, R 1 , and R 4 through R 7 are defined as in the specification, processes for preparing the same and intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.

  这项发明涉及公式1的化合物 其中G、D、A、Z、Q、X、Y、R 1 和R 4 至R 7 的定义如规范中所述，制备这些化合物的方法以及用于制备这些化合物的中间体，以及含有这些化合物的药物组合物及其在治疗中枢神经系统疾病和其他疾病中的用途。
• [EN] 5-[3-[PIPERAZIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS<br/>[FR] DÉRIVÉS DE 5-[3-[PIPÉRAZIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE À UTILISER EN TANT QU'INHIBITEURS D'ADAMTS 4 ET 5 POUR TRAITER PAR EXEMPLE L'ARTHROSE
  申请人：GALAPAGOS NV

  公开号：WO2017211666A1

  公开（公告）日：2017-12-14

  The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.

  本发明公开了根据式(I)的5-[3-[哌嗪-1-基]-3-氧代-丙基]-咪唑啉-2,4-二酮衍生物，其中R1、R2、R3a、R3b、R6a、R6b、下标n和Cy如本文所定义。本发明涉及抑制ADAMTS 4和5的化合物，用于预防或治疗炎症性疾病或涉及软骨降解或破坏软骨稳态的疾病，例如骨关节炎。
• 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。
• [EN] [1,8]NAPHTHYRIDIN-2-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA<br/>[FR] [1,8]NAPHTYRIDIN-2-ONES ET COMPOSES APPARENTES DESTINES AU TRAITEMENT DE LA SCHIZOPHRENIE
  申请人：WARNER LAMBERT CO

  公开号：WO2005019215A1

  公开（公告）日：2005-03-03

  This invention relates to compounds of the Formula (1) wherein G, A, Z, Q, X, Y, and R1 and R2 are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system and other disorders.

  本发明涉及式（1）的化合物，其中G，A，Z，Q，X，Y和R1和R2如规范中所定义，包含它们的制药组合物以及它们在治疗中枢神经系统和其他疾病中的应用。