3,3,6-trimethyl-2,5-piperazinedione | 66449-54-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3,3,6-trimethyl-2,5-piperazinedione
• 英文别名: 3,3,6-trimethyl-piperazine-2,5-dione；3,3,6-Trimethylpiperazine-2,5-dione
• CAS: 66449-54-5
• 化学式: C₇H₁₂N₂O₂
• 分子量: 156.184
• InChiKey: QWLLBIAYORQXSC-UHFFFAOYSA-N

物化性质

• 沸点：
  418.9±38.0 °C(Predicted)
• 密度：
  1.041±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,3,6-trimethyl-2,5-piperazinedione 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 2,5,5-三甲基哌嗪-1-羧酸叔丁酯
  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：

  Boc-Aib-Ala-OMe 在 甲酸 作用下， 以 仲丁醇 为溶剂， 反应 18.0h， 生成 3,3,6-trimethyl-2,5-piperazinedione
  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

• H-Atom abstraction by C-centered radicals from cyclic and acyclic dipeptides. A theoretical and experimental study of reaction rates
  作者：Darren L. Reid、David A. Armstrong、Arvi Rauk、Chandrasekhar Nese、Man Nien Schuchmann、Ursula Westhoff、Clemens von Sonntag

  DOI：10.1039/b303223j

  日期：——

  Using the pulse radiolysis and other radiation chemical techniques, the reaction kinetics of ˙CH3 and ˙CH2OH radicals with alanine anhydride, glycine anhydride and sarcosine anhydride were examined in aqueous solution. The second order rate constant of reaction of ˙CH3 with alanine anhydride has been determined at 2 × 105 dm3 mol−1 s−1. A very similar value (8 × 104 dm3 mol−1 s−1) has been obtained

  利用脉冲辐解和其他辐射化学技术，研究了˙CH3和˙CH2OH自由基与丙氨酸酐、甘氨酸酐和肌氨酸酐在水溶液中的反应动力学。˙ 与丙氨酸酐反应的二级速率常数已确定为 2 × 105 dm3 mol-1 s-1。通过测量甲烷和乙烷产率作为不同剂量率下丙氨酸酐浓度的函数并通过计算机分析评估这些数据，获得了非常相似的值 (8 × 104 dm3 mol-1 s-1)。用甘氨酸酐和肌氨酸酐进行的类似实验对这些化合物产生了相同的速率常数，均为 4 × 104 dm3 mol-1 s-1。发现˙CH2OH自由基不与丙氨酸酐以可观的速率反应（k < 2 × 102 dm3 mol-1 s-1）。通过B3LYP/6-311+G(d,p)理论水平的理论计算研究了˙ 、˙CH2OH和˙C( )2OH与环状酸酐和无环甘氨酸和丙氨酸肽的反应. 气相中的自由能在经典的谐振子-刚性转子模型中确定，并用于估计肽的αC位点的氢转移反应速率。通过