tert-butyl 4-(thiophene-2-carbonyl)-1,4-diazepane-1-carboxylate | 877061-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: tert-butyl 4-(thiophene-2-carbonyl)-1,4-diazepane-1-carboxylate
• CAS: 877061-08-0
• 化学式: C₁₅H₂₂N₂O₃S
• 分子量: 310.417
• InChiKey: IORDBNGODLTISU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(thiophene-2-carbonyl)-1,4-diazepane-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到1,4-二叠氮烷-1-基(2-噻吩)甲酮
  参考文献：
  名称：

  Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands

  摘要：

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.

  DOI：

  10.1021/acsmedchemlett.9b00524
• 作为产物：
  描述：

  2-噻吩甲酰氯 、 1,4-二氮杂环庚烷-1-甲酸叔丁酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到tert-butyl 4-(thiophene-2-carbonyl)-1,4-diazepane-1-carboxylate
  参考文献：
  名称：

  Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands

  摘要：

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.

  DOI：

  10.1021/acsmedchemlett.9b00524

文献信息

• Synthesis, Cytotoxicity Evaluation, and Computational Insights of Novel 1,4-Diazepane-Based Sigma Ligands
  作者：Daniele Zampieri、Sara Fortuna、Antonella Calabretti、Maurizio Romano、Renzo Menegazzi、Dirk Schepmann、Bernhard Wünsch、Maria Grazia Mamolo

  DOI：10.1021/acsmedchemlett.9b00524

  日期：2020.5.14

  Among several potential applications, sigma receptor ligands can be used as antipsychotics, antiamnesics, and against other neurodegenerative disorders as well as neuroprotective agents. We present herein a new series of diazepane-containing derivatives as sigma R ligands obtained by a conformational expansion approach of our previously synthesized piperidine-based compounds. The best results were reached by benzofurane 2c, 3c and quinoline 2d, 3d-substituted diazepane derivatives, which showed the highest sigma R affinity. The cytotoxic activities of synthesized compounds were evaluated against two cancer cell lines, and the results indicated that none of the compounds induced significant toxicity in these cells. We also evaluated the antioxidant activity by radical scavenging capacity of our best compounds on ABTS and H2O2. The results obtained reveal that our new derivatives possess an excellent antioxidant profile and could be protective for the cells. Overall, the benzofurane derivative 2c due to its strong interaction with the active site of the receptor, as confirmed by molecular dynamic simulations, emerged as the optimum compound with high sigma 1R affinity, low cytotoxicity, and a potent antioxidant activity.