4-(2,3-二氯苯基)-1-哌嗪乙醇 | 90096-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(2,3-二氯苯基)-1-哌嗪乙醇
• 英文名称: 2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethan-1-ol
• 英文别名: 2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanol；4-(2,3-Dichlorophenyl)-1-piperazineethanol；2-[4-(2,3-Dichlorophenyl)piperazin-1-yl]ethan-1-ol；2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethanol
• CAS: 90096-40-5
• 化学式: C₁₂H₁₆Cl₂N₂O
• 分子量: 275.178
• InChiKey: HMSZCGYHVDSIIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2,3-二氯苯基)-1-哌嗪乙醇 以 异丙醇 为溶剂， 生成 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylic acid methyl ester 2-(N-4-(2,3-dichlorophenyl)piperazinyl)ethyl ester
  参考文献：
  名称：

  具有强效和持久降压作用的新型1,4-二氢吡啶衍生物。

  摘要：

  在寻找对心血管系统具有长效作用的新的1,4-二氢吡啶衍生物时，合成并测试了一系列在哌嗪环的4-氮上带有亲脂性取代基的吡哆酯类化合物I对自发性高血压大鼠(SHR)的降压效果。化合物I，尤其是那些在哌嗪环上有二苯甲基部分的化合物，显示出极其强大且长效的降压特性。还制备了与I相关的类似物，并讨论了结构-活性关系。

  DOI：

  10.1248/cpb.33.3787
• 作为产物：
  描述：

  1-(2,3-二氯苯基)哌嗪 、 2-溴乙醇 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以58%的产率得到4-(2,3-二氯苯基)-1-哌嗪乙醇
  参考文献：
  名称：

  Molecular Determinants of Selectivity and Efficacy at the Dopamine D3 Receptor

  摘要：

  The dopamine D3 receptor (D3R) has been implicated in substance abuse and other neuropsychiatric disorders. The high sequence homology between the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has made the development of D3R-selective compounds challenging. Here, we deconstruct into pharmacophoric elements a series of D3R-selective substituted-4-phenylpiperazine compounds and use computational simulations and binding and activation studies to dissect the structural bases for D3R selectivity and efficacy. We find that selectivity arises from divergent interactions within a second binding pocket (SBP) separate from the OBS, whereas efficacy depends on the binding mode in the OBS. Our findings reveal structural features of the receptor that are critical to selectivity and efficacy that can be used to design highly D3R-selective ligands with targeted efficacies. These findings are generalizable to other GPCRs in which the SBP can be targeted by bitopic or allosteric ligands.

  DOI：

  10.1021/jm300482h

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] MEDICAMENTS<br/>[FR] MÉDICAMENTS
  申请人：MOTAC NEUROSCIENCE LTD

  公开号：WO2009056805A1

  公开（公告）日：2009-05-07

  A compound of formula (I) is described: wherein R1 and R2 are as defined in the text and wherein the compounds are intended for use in treating medical conditions characterized by an imbalance in dopamine receptor activity.

  描述了一种化合物的化学式(I)：其中R1和R2如文本中定义的那样，这些化合物旨在用于治疗以多巴胺受体活性失衡为特征的医疗状况。
• Novel Dual-Target μ-Opioid Receptor and Dopamine D₃ Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management
  作者：Alessandro Bonifazi、Francisco O. Battiti、Julie Sanchez、Saheem A. Zaidi、Eric Bow、Mariia Makarova、Jianjing Cao、Anver Basha Shaik、Agnieszka Sulima、Kenner C. Rice、Vsevolod Katritch、Meritxell Canals、J. Robert Lane、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.1c00611

  日期：2021.6.10

  safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopamine D3 receptor (D3R) with highly selective antagonists/partial agonists can reduce opioid self-administration and reinstatement to drug seeking in rodent models without

  对更安全的疼痛管理疗法和减少滥用倾向的需求激发了一种新的药物设计，该药物设计保留了 μ-阿片受体 (MOR) 介导的镇痛作用，同时最大限度地减少了成瘾倾向。我们最近证明，用高选择性拮抗剂/部分激动剂靶向多巴胺 D 3受体 (D 3 R) 可以减少阿片类药物的自我给药和在啮齿动物模型中恢复药物寻求，而不会降低镇痛作用。将 D 3 R 确定为治疗阿片类药物使用障碍的靶点促使产生一类呈现双位或二价结构的配体的想法，允许 MOR 和 D 3的双靶点结合R. 使用计算辅助药物设计和体外结合试验的结构-活性关系研究导致基于不同的结构模板和支架，具有中等（亚微摩尔) 到高（低纳摩尔/亚纳摩尔）结合亲和力。基于生物发光共振能量转移的功能研究揭示了 MOR 激动剂-D 3 R 拮抗剂/部分激动剂的功效，这表明具有维持镇痛作用并降低阿片类药物滥用倾向的潜力。
• [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。
• [1,8]NAPHTHYRIDIN-2-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA
  申请人：Clark D. Jerry

  公开号：US20060287310A1

  公开（公告）日：2006-12-21

  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.

  本发明涉及式1的化合物，其中G、D、A、Z、Q、X、Y、R1和R4至R7如规范中所定义，制备该化合物的过程以及用于制备该化合物的中间体，以及含有该化合物的制药组合物及其在治疗中枢神经系统疾病和其他疾病中的应用。