(2S,2′S)-tetramethyl 2,2′-((2,2′-diselanediylbis(benzoyl))bis(azanediyl))disuccinate

• 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: (2S,2′S)-tetramethyl 2,2′-((2,2′-diselanediylbis(benzoyl))bis(azanediyl))disuccinate
• 英文别名: dimethyl (2S)-2-[[2-[[2-[[(2S)-1,4-dimethoxy-1,4-dioxobutan-2-yl]carbamoyl]phenyl]diselanyl]benzoyl]amino]butanedioate
• 化学式: C₂₆H₂₈N₂O₁₀Se₂
• 分子量: 686.436
• InChiKey: NVKNRVXXGOGONF-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.37
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S,2′S)-tetramethyl 2,2′-((2,2′-diselanediylbis(benzoyl))bis(azanediyl))disuccinate 在 碘 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以99%的产率得到(S)-dimethyl 2-(3-oxobenzo[d][1,2]selenazol-2(3H)-yl)succinate
  参考文献：
  名称：

  通过理论研究将邻氨基芳基二硒化物快速轻松地转化为相应的依布硒啉类衍生物

  摘要：

  对酰胺基芳基二硒化物作为亲电衍生物进行的DFT计算表明，当硒键合到硒原子（二硒化物），溴原子（硒烯基溴化物）和O原子（硒酸）上时，存在普遍的Se⋯O弱相互作用。碘化物衍生物，预测了Se⋯N相互作用的普遍贡献。考虑到依布硒仑的药理学相关性，最近也报道了依伯硒仑的药理学意义，已通过实验对这种计算机模拟观察结果进行了有效的合成，以合成一个小的N-取代苯并异噻唑-3（2 H）-和苯并异噻唑-3（2 H）-的小文库。抗Sars-Cov2的抗病毒剂。

  DOI：

  10.1039/d0nj01605e
• 作为产物：
  描述：

  双（2-羧基苯基）二硒化物 、 L-天冬氨酸二甲酯盐酸盐 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 8.67h， 以63%的产率得到(2S,2′S)-tetramethyl 2,2′-((2,2′-diselanediylbis(benzoyl))bis(azanediyl))disuccinate
  参考文献：
  名称：

  Design and Synthesis of DiselenoBisBenzamides (DISeBAs) as Nucleocapsid Protein 7 (NCp7) Inhibitors with anti-HIV Activity

  摘要：

  The interest in the synthesis of Se-containing compounds is growing with the discovery of derivatives exhibiting various biological activities. In this manuscript, we have identified a series of 2,2'-diselenobisbenzamides (DISeBAs) as novel HIV retroviral nucleocapsid protein 7 (NCp7) inhibitors. Because of its pleiotropic functions in the whole viral life cycle and its mutation intolerant nature, NCp7 represents a target of great interest which is not reached by any anti-HIV agent in clinical use. Using the diselenobisbenzoic scaffold, amino acid, and benzenesulfonamide derivatives were prepared and biologically profiled against different models of HIV infection. The incorporation of amino acids such as glycine and glutamate into DISeBAs 7 and 8 resulted in selective anti-HIV activity against both acutely and chronically infected cells as well as an interesting virucidal effect. DISeBAs demonstrated broad antiretroviral activity, encompassing HIV-1 drug-resistant strains including clinical isolates, as well as simian immunodeficiency virus (SW). Time of addition experiments, along with the observed dose dependent inhibition of the Gag precursor proper processing, confirmed that their mechanism of action is based on NCp7 inhibition.

  DOI：

  10.1021/acs.jmedchem.5b01183

文献信息

• Design and Synthesis of DiselenoBisBenzamides (DISeBAs) as Nucleocapsid Protein 7 (NCp7) Inhibitors with anti-HIV Activity
  作者：Luca Sancineto、Alice Mariotti、Luana Bagnoli、Francesca Marini、Jenny Desantis、Nunzio Iraci、Claudio Santi、Christophe Pannecouque、Oriana Tabarrini

  DOI：10.1021/acs.jmedchem.5b01183

  日期：2015.12.24

  The interest in the synthesis of Se-containing compounds is growing with the discovery of derivatives exhibiting various biological activities. In this manuscript, we have identified a series of 2,2'-diselenobisbenzamides (DISeBAs) as novel HIV retroviral nucleocapsid protein 7 (NCp7) inhibitors. Because of its pleiotropic functions in the whole viral life cycle and its mutation intolerant nature, NCp7 represents a target of great interest which is not reached by any anti-HIV agent in clinical use. Using the diselenobisbenzoic scaffold, amino acid, and benzenesulfonamide derivatives were prepared and biologically profiled against different models of HIV infection. The incorporation of amino acids such as glycine and glutamate into DISeBAs 7 and 8 resulted in selective anti-HIV activity against both acutely and chronically infected cells as well as an interesting virucidal effect. DISeBAs demonstrated broad antiretroviral activity, encompassing HIV-1 drug-resistant strains including clinical isolates, as well as simian immunodeficiency virus (SW). Time of addition experiments, along with the observed dose dependent inhibition of the Gag precursor proper processing, confirmed that their mechanism of action is based on NCp7 inhibition.
• Fast and easy conversion of <i>ortho</i> amidoaryldiselenides into the corresponding ebselen-like derivatives driven by theoretical investigations
  作者：Vanessa Nascimento、Pâmella Silva Cordeiro、Massimiliano Arca、Francesca Marini、Luca Sancineto、Antonio Luiz Braga、Vito Lippolis、Michio Iwaoka、Claudio Santi

  DOI：10.1039/d0nj01605e

  日期：——

  acid), while for selenenyl iodide derivatives, a prevalent contribution of the Se⋯N interaction was predicted. This in silico observation has been experimentally exploited for the efficient synthesis of a small library of N-substituted benzoisoselenazol-3(2H)-ones and benzoisothiazol-3(2H)-ones considering the pharmacological relevance of ebselen recently reported also as an antiviral agent against Sars-Cov2

  对酰胺基芳基二硒化物作为亲电衍生物进行的DFT计算表明，当硒键合到硒原子（二硒化物），溴原子（硒烯基溴化物）和O原子（硒酸）上时，存在普遍的Se⋯O弱相互作用。碘化物衍生物，预测了Se⋯N相互作用的普遍贡献。考虑到依布硒仑的药理学相关性，最近也报道了依伯硒仑的药理学意义，已通过实验对这种计算机模拟观察结果进行了有效的合成，以合成一个小的N-取代苯并异噻唑-3（2 H）-和苯并异噻唑-3（2 H）-的小文库。抗Sars-Cov2的抗病毒剂。