2,2,5-三甲基哌嗪 | 139139-56-3

• 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: 2,2,5-三甲基哌嗪
• 英文名称: 2,2,5-trimethylpiperazine
• CAS: 139139-56-3
• 化学式: C₇H₁₆N₂
• 分子量: 128.217
• InChiKey: BHUBBXYEMNDWPZ-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  168.2±8.0 °C(Predicted)
• 密度：
  0.817±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2,5-三甲基哌嗪 在 potassium carbonate 、 三氟乙酸 作用下， 以 水 、 乙腈 为溶剂， 反应 100.0h， 生成 N,N-Diethyl-4-[(3-methoxy-phenyl)-(2,2,5-trimethyl-piperazin-1-yl)-methyl]-benzamide
  参考文献：
  名称：

  New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability

  摘要：

  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.

  DOI：

  10.1021/jm000228x
• 作为产物：
  描述：

  3,3,6-trimethyl-2,5-piperazinedione 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以84%的产率得到2,2,5-三甲基哌嗪
  参考文献：
  名称：

  New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability

  摘要：

  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.

  DOI：

  10.1021/jm000228x

文献信息

• Alkyl substituted piperazines as chain extenders in polyurea elastomer
  申请人：Texaco Chemical Company

  公开号：US05171819A1

  公开（公告）日：1992-12-15

  A polyurea elastomer is disclosed. The elastomer includes an isocyanate, an amine terminated polyoxyalkylene polyol, and a chain extender. The isocyanate is preferably a quasi-prepolymer of an isocyanate and a material selected from at least one polyol, a high molecular weight polyoxyalkyleneamine or a combination thereof. The chain extender includes at least an alkyl substituted piperazine.

  本发明揭示了一种聚氨酯弹性体。该弹性体包括异氰酸酯、末端胺基聚氧烷基聚醚醇和链延长剂。所述异氰酸酯优选为异氰酸酯和至少一种聚醇、高分子量聚氧烷基胺或其组合物的准预聚物。所述链延长剂包括至少一种烷基取代哌嗪。
• Alkyl substituted piperazines and use as chain extenders in polyurea elastomer systems
  申请人：TEXACO CHEMICAL COMPANY

  公开号：EP0459692A2

  公开（公告）日：1991-12-04

  A useful group of chain extenders for the production of polyurea elastomers by reacting polyisocyanates with amine-terminated polyols are alkyl-substituted piperazines. The preferred piperazines, some of which are novel, are compounds of the formula wherein R is C₁-C₁₀ alkyl and R′ and R˝ are each alkyl radical or inertly-substituted alkyl. These alkyl-substituted piperazines can be obtained by reacting a 2-amino-2-alkyl-1-alkanol alkylene oxide adduct with ammonia.

  通过多异氰酸酯与胺封端多元醇反应生产聚脲弹性体的一类有用的扩链剂是烷基取代的哌嗪。优选的哌嗪（其中一些是新型的）是如下式的化合物 其中 R 是 C₁-C₁₀ 烷基，R′ 和 R˝ 分别是烷基或惰性取代的烷基。 这些烷基取代的哌嗪可以通过 2-氨基-2-烷基-1-烷醇氧化亚烷基加合物与氨反应获得。
• US5171819A
  申请人：——

  公开号：US5171819A

  公开（公告）日：1992-12-15
• 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.