4-(dimethylamino)-N,N-dimethyl-2,2-diphenylbutanamide | 94682-46-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(dimethylamino)-N,N-dimethyl-2,2-diphenylbutanamide
• 英文别名: 4-dimethylamino-N,N-dimethyl-2,2-diphenyl-butyramide；4-dimethylamino-N,N-dimethyl-2,2-diphenylbutyramide；AB06-114；4-dimethylamino-2,2-diphenyl-butyric acid dimethylamide；4-Dimethylamino-2,2-diphenyl-buttersaeure-dimethylamid
• CAS: 94682-46-9
• 化学式: C₂₀H₂₆N₂O
• 分子量: 310.439
• InChiKey: PCDNISCTQCOCTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  溴甲烷 、 4-(dimethylamino)-N,N-dimethyl-2,2-diphenylbutanamide 在 丁酮 作用下， 生成 (3-dimethylcarbamoyl-3,3-diphenyl-propyl)-trimethyl-ammonium; bromide
  参考文献：
  名称：

  Moffett; Aspergren, Journal of the American Chemical Society, 1957, vol. 79, p. 4462,4464, 4465

  摘要：

  DOI：
• 作为产物：
  描述：

  双苯酰草胺 、 2-氯-N,N-二甲基乙胺 在 sodium amide 、 甲苯 作用下， 生成 4-(dimethylamino)-N,N-dimethyl-2,2-diphenylbutanamide
  参考文献：
  名称：

  Moffett; Aspergren, Journal of the American Chemical Society, 1957, vol. 79, p. 4462,4464, 4465

  摘要：

  DOI：

文献信息

• 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] DUAL-TARGET MU OPIOID AND DOPAMINE D3 RECEPTORS LIGANDS; PREPARATION AND USE THEREOF<br/>[FR] LIGANDS À DOUBLE CIBLE DES RÉCEPTEURS DES OPIACÉS MU ET DOPAMINERGIQUES D3 ; PRÉPARATION ET UTILISATION CORRESPONDANTS
  申请人：US HEALTH

  公开号：WO2022187206A1

  公开（公告）日：2022-09-09

  Disclosed herein are novel dual-target compounds that bind at both the mu-opioid receptor (MOR) and dopamine D3receptors (D3R) to provide MOR-mediated analgesia, while minimizing addictive liability through D3R antagonism/partial agonism. The novel compounds are useful in the treatment of pain and substance use disorder.

  本文披露了一种新型的双靶点化合物，它们能够同时结合μ-阿片受体（MOR）和多巴胺D3受体（D3R），从而通过D3R的拮抗/部分激动作用来最小化成瘾性，同时提供MOR介导的镇痛作用。这种新型化合物可用于治疗疼痛和物质使用障碍。
• Phase behaviour analysis of solid dispersions of loperamide and two structurally related compounds with the polymers PVP-K30 and PVP-VA64
  作者：Ilse Weuts、Dieter Kempen、Annelies Decorte、Geert Verreck、Jef Peeters、Marcus Brewster、Guy Van den Mooter

  DOI：10.1016/j.ejps.2004.04.002

  日期：2004.8

  The purpose of the present study was to investigate the influence of the structure of a poorly water soluble model drug (loperamide) on the phase behaviour in solid dispersions with PVP-K30. Dispersions with PVP-VA64, a less hydrophilic polymer, were investigated as well in order to study the influence of differences in polymer structure and water content of the samples. The solid dispersions of PVP-K30 or PVP-VA64 with loperamide as well as with two fragments of this molecule were prepared by spray drying. The amount of residual solvents and water was determined with GC and thermogravimetric analysis (TGA). The drug loading of the dispersions was determined using high performance liquid chromatography (HPLC). The solid state properties were evaluated using powder-XRD, IR-spectroscopy and MT-DSC. All mixtures containing loperamide proved to be completely amorphous, whereas the dispersions containing the fragments are only amorphous in case the polymer content is high. The phase diagrams that were constructed clearly show that loperamide exhibits a different behaviour in the solid dispersions than its two building blocks. They also point to the presence of specific intermolecular compound-polymer interactions in the dispersions of one of the fragments with the two polymers. This was confirmed by the IR-results. Despite structural similarities, interactions in dispersions containing loperamide are far less important. In dispersions containing high concentrations of the other fragment, the DSC curves give indications for polymorphism whereas IR and XRD-spectra point towards inclusion of solvent in these samples. (C) 2004 Elsevier B.V. All rights reserved.
• Moffett; Aspergren, Journal of the American Chemical Society, 1957, vol. 79, p. 4462,4464, 4465
  作者：Moffett、Aspergren

  DOI：——

  日期：——