4-[(4-Allyl-piperazin-1-yl)-phenyl-methyl]-N,N-diethyl-benzamide | 229162-13-4

• 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-[(4-Allyl-piperazin-1-yl)-phenyl-methyl]-N,N-diethyl-benzamide
• 英文别名: N,N-diethyl-4-[phenyl-(4-prop-2-enylpiperazin-1-yl)methyl]benzamide
• CAS: 229162-13-4
• 化学式: C₂₅H₃₃N₃O
• 分子量: 391.557
• InChiKey: PAIJMERJJOWHIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-苯甲酰苯甲酸 在 sodium tetrahydroborate 、 REM resin 、 三溴化磷 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[(4-Allyl-piperazin-1-yl)-phenyl-methyl]-N,N-diethyl-benzamide
  参考文献：
  名称：

  Synthesis of novel analogues of the delta opioid ligand SNC-80 using REM resin

  摘要：

  Focused libraries of delta opioid ligands were synthesised using REM resin methodology. Several high affinity compounds were identified with good selectivity over the mu opioid receptor. Automated REM resin recycling was used to synthesise larger amounts of ligand for in vivo studies. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00173-0

文献信息

• Probes for Narcotic Receptor Mediated Phenomena. 26. Synthesis and Biological Evaluation of Diarylmethylpiperazines and Diarylmethylpiperidines as Novel, Nonpeptidic δ Opioid Receptor Ligands
  作者：Xiaoyan Zhang、Kenner C. Rice、Silvia N. Calderon、Hiroshi Kayakiri、Larren Smith、Andrew Coop、Arthur E. Jacobson、Richard B. Rothman、Peg Davis、Christina M. Dersch、Frank Porreca

  DOI：10.1021/jm9903895

  日期：1999.12.1

  bound to the delta receptor with K(i) values in the low nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were negligible, indicating excellent delta opioid receptor subtype selectivity. The two nitrogen atoms on the piperazine nucleus showed different SAR in the interaction of this series of compounds at the delta receptor. Nitrogen N(4) appears

  我们最近报道了（+）-4-？（alphaR）-alpha-？（2S，5R）-4-烯丙基-2，5-二甲基-1-哌嗪基??-3-甲氧基苄基-N，N-二乙基苯甲酰胺（1b， SNC80）作为一种新型的非肽δ受体激动剂，并探索了一系列相关衍生物的构效关系（SAR）。我们发现当1b中的3-甲氧基被其他取代基取代或取代时，δ结合活性和选择性几乎没有变化，而N，N-二乙基苯甲酰胺基对于与δ受体的相互作用很重要。哌嗪核的广泛修饰导致合成了一系列新的N，N-二乙基（α-哌嗪基苄基）苯甲酰胺（2，3a-e），N，N-二乙基（α-哌啶基或哌啶亚基苄基）苯甲酰胺（4a， 5a-c，6a-b）和相关派生词（4b，7a-c）。几种化合物（2，3a，3e，6a）以低纳摩尔范围内的K（i）值牢固结合至δ受体。另一方面，这些化合物对mu和κ受体的结合亲和力可忽略不计，表明优异的δ阿片样物质受体亚型选择性。在该系列化合物在δ
• New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability
  作者：Niklas Plobeck、Daniel Delorme、Zhong-Yong Wei、Hua Yang、Fei Zhou、Peter Schwarz、Lars Gawell、Hélène Gagnon、Benjamin Pelcman、Ralf Schmidt、Shi Yi Yue、Christopher Walpole、William Brown、Edward Zhou、Maryse Labarre、Kemal Payza、Stephane St-Onge、Augustus Kamassah、Pierre-Emmanuel Morin、Denis Projean、Julie Ducharme、Edward Roberts

  DOI：10.1021/jm000228x

  日期：2000.10.1

  Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl( 1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC50 = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)- methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, mu/delta = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.
• Synthesis of novel analogues of the delta opioid ligand SNC-80 using AlCl3-promoted aminolysis
  作者：D.R Barn、A Bom、J Cottney、W.L Caulfield、J.R Morphy

  DOI：10.1016/s0960-894x(99)00174-2

  日期：1999.5

  Two focused libraries of delta opioid ligands were synthesised using AlCl3 facilitated aminolysis. Several compounds were identified with DOR binding affinities higher or similar to SNC-IO. A novel acyclic derivative of SNC-80 produced antinociception in the acetic acid abdominal constriction test, which is at least partially mediated via the delta-opioid receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.
• NOVEL COMPOUNDS WITH ANALGESIC EFFECT
  申请人：Astra Pharma Inc.

  公开号：EP0915855A1

  公开（公告）日：1999-05-19