1,4-bis(phenylsulfonyl)tetrahydropyrazine-2,5-dione | 33295-34-0

• 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: 1,4-bis(phenylsulfonyl)tetrahydropyrazine-2,5-dione
• 英文别名: 1,4-bis(phenylsulfonyl)piperazine-2,5-dione；1.4-Diphenylsulfon-2.5-dioxo-piperazin；1,4-bis-benzenesulfonyl-piperazine-2,5-dione；1,4-bis(benzenesulfonyl)piperazine-2,5-dione
• CAS: 33295-34-0
• 化学式: C₁₆H₁₄N₂O₆S₂
• 分子量: 394.429
• InChiKey: NHASEHCTEAENPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  苯磺酰基氨基乙酸 以 乙二醇 为溶剂， 以40%的产率得到1,4-bis(phenylsulfonyl)tetrahydropyrazine-2,5-dione
  参考文献：
  名称：

  Development of Piperazinediones as dual inhibitor for treatment of Alzheimer's disease

  摘要：

  Novel multifunctional 3,6-Diphenyl-1,4-bis(phenylsulfonyl)piperazine-2,5-dione derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). The designed scaffold has blood brain barrier penetrating ability, acetylcholinesterase (AChE) and matrix metalloproteinase-2 (MMP-2) inhibition potential. Compounds 52 and 46 showed very significant inhibition against AChE, IC50 = 32.45 +/- 0.044, 28.65 +/- 0.029, BuChE, IC50 = 157.95 +/- 0.264, 160.58 +/- 0.082 and MMP-2, IC50 = 36.83 +/- 0.015, 19.57 +/- 0.005 (nM). In the enzyme kinetics study, lead molecule 46 showed noncompetitive inhibition of AChE with K-i = 7 nM and competitive inhibition of MMP-2 with K-i = 20 nM. Compounds 52 and 46 inhibited AChE-induced A beta aggregation at 20 mu M. The compounds also exhibited in-vitro antioxidant potential in DPPH assay. Further, compound 46 was found to be a promising neuroprotective agent in MC65 cells. Lead molecule 46 significantly enhanced working memory in scopolamine induced amnesia animal model at dose of 5 mg/kg dose. The mitochondrial membrane potential was restored in animals when treated with compounds 52 and 46. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.078

文献信息

• A Simple Approach to the Synthesis of 1,4-Bis(arylsulfonyl)tetrahydropyrazine-2,5-diones
  作者：Issa Yavari、Abdolali Alizadeh

  DOI：10.1007/s00706-002-0533-4

  日期：2003.2.1

  The addition of triphenylphosphine to dimethyl acetylenedicarboxylate in the presence of arylsulfonylglycyl chlorides leads to 1,4-bis-arylsulfonyl-tetrahydropyrazine-2,5-diones and dimethyl (E)-2-chloro-2-butenedioate.
• Development of Piperazinediones as dual inhibitor for treatment of Alzheimer's disease
  作者：Devendra Kumar、Sukesh K. Gupta、Ankit Ganeshpurkar、Gopichand Gutti、Sairam Krishnamurthy、Gyan Modi、Sushil K. Singh

  DOI：10.1016/j.ejmech.2018.02.078

  日期：2018.4

  Novel multifunctional 3,6-Diphenyl-1,4-bis(phenylsulfonyl)piperazine-2,5-dione derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). The designed scaffold has blood brain barrier penetrating ability, acetylcholinesterase (AChE) and matrix metalloproteinase-2 (MMP-2) inhibition potential. Compounds 52 and 46 showed very significant inhibition against AChE, IC50 = 32.45 +/- 0.044, 28.65 +/- 0.029, BuChE, IC50 = 157.95 +/- 0.264, 160.58 +/- 0.082 and MMP-2, IC50 = 36.83 +/- 0.015, 19.57 +/- 0.005 (nM). In the enzyme kinetics study, lead molecule 46 showed noncompetitive inhibition of AChE with K-i = 7 nM and competitive inhibition of MMP-2 with K-i = 20 nM. Compounds 52 and 46 inhibited AChE-induced A beta aggregation at 20 mu M. The compounds also exhibited in-vitro antioxidant potential in DPPH assay. Further, compound 46 was found to be a promising neuroprotective agent in MC65 cells. Lead molecule 46 significantly enhanced working memory in scopolamine induced amnesia animal model at dose of 5 mg/kg dose. The mitochondrial membrane potential was restored in animals when treated with compounds 52 and 46. (C) 2018 Elsevier Masson SAS. All rights reserved.