PG648 | 1092953-69-9

• 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: PG648
• 英文别名: US8748608, 34 Enantiomer A；N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxybutyl]-1H-indole-2-carboxamide
• CAS: 1092953-69-9
• 化学式: C₂₃H₂₆Cl₂N₄O₂
• 分子量: 461.391
• InChiKey: NABHHUMHJIHHIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  71.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-amino-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)butan-2-ol 、 吲哚-2-羧酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以72%的产率得到PG648
  参考文献：
  名称：

  N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists

  摘要：

  In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl- and 2-OCH3-phenylpiperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (K-i = 1 nM) for D3 and similar to 400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors, further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders.

  DOI：

  10.1021/jm900095y

文献信息

• [EN] DOPAMINE D3 RECEPTOR SELECTIVE ANTAGONISTS/PARTIAL AGONISTS; METHOD OF MAKING; AND USE THEREOF<br/>[FR] ANTAGONISTES/AGONISTES PARTIELS SÉLECTIFS DU RÉCEPTEUR D3 DE LA DOPAMINE ; PROCÉDÉ DE PRÉPARATION ; ET UTILISATION ASSOCIÉE
  申请人：US HEALTH

  公开号：WO2017160552A1

  公开（公告）日：2017-09-21

  Disclosed herein novel dopamine D3 receptor selective antagonists/partial agonists compounds with high affinity and metabolic stability useful for the treatment of psychiatric and neurological disorders and as research and diagnostic tools. Also disclosed are methods of making the compounds.

  本文披露了一种新型多巴胺D3受体选择性拮抗剂/部分激动剂化合物，具有高亲和力和代谢稳定性，可用于治疗精神疾病和神经系统疾病，并作为研究和诊断工具。还披露了制备这些化合物的方法。
• 4-PHENYLPIPERAZINE DERIVATIVES WITH FUNCTIONALIZED LINKERS AS DOPAMINE D3 RECEPTOR SELECTIVE LIGANDS AND METHODS OF USE
  申请人：Newman Amy Hauck

  公开号：US20100267737A1

  公开（公告）日：2010-10-21

  Dopamine D 3 receptor antagonists and partial agonists are known to modulate the reinforcing and drug-seeking effects induced by cocaine and other abused substances. By introducing functionality into the butylamide linking chain of the 4-phenylpiperazine class of ligands, improved D 3 receptor affinity and selectivity, as well as water solubility, is achieved. A series of linking-chain derivatives are disclosed wherein functionality such as OH or OAc groups have been introduced into the linking chain. In general, these modifications are well tolerated at D 3 receptors and achieve high selectivity over D 2 and D 4 receptors.

  多巴胺D3受体拮抗剂和部分激动剂已知可以调节可卡因和其他滥用物质引起的强化和寻药效应。通过在4-苯基哌嗪类配体的丁酰胺链中引入功能基团，可以获得改进的D3受体亲和力和选择性，以及水溶性。公开了一系列链连接衍生物，其中引入了OH或OAc基团等功能基团。一般来说，这些修饰在D3受体上很好地耐受，并实现了对D2和D4受体的高选择性。
• Dopamine D3 receptor selective antagonists/partial agonists; method of making; and use thereof
  申请人：THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：US11299476B2

  公开（公告）日：2022-04-12

  Disclosed herein novel dopamine D3 receptor selective antagonists/partial agonists compounds with high affinity and metabolic stability useful for the treatment of psychiatric and neurological disorders and as research and diagnostic tools. Also disclosed are methods of making the compounds.

  本披露内容涉及一种新型的高亲和力和代谢稳定的大麻素D3受体选择性拮抗剂/部分激动剂化合物，这些化合物可用于治疗精神和神经系统疾病，以及作为研究和诊断工具。同时，本披露还涉及制备这些化合物的方法。
• DOPAMINE D3 RECEPTOR SELECTIVE ANTAGONISTS/PARTIAL AGONISTS; METHOD OF MAKING; AND USE THEREOF
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：EP3429993B1

  公开（公告）日：2021-05-26
• US8748608B2
  申请人：——

  公开号：US8748608B2

  公开（公告）日：2014-06-10