O²-2-bromoethyl pyrrolidinyl diazen-1-ium-1,2-diolate | 191083-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: O²-2-bromoethyl pyrrolidinyl diazen-1-ium-1,2-diolate
• 英文别名: 2-bromoethoxyimino-oxido-pyrrolidin-1-ylazanium
• CAS: 191083-57-5
• 化学式: C₆H₁₂BrN₃O₂
• 分子量: 238.084
• InChiKey: VMSWMPULBDPNBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.29
• 重原子数：
  12.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  50.9
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  O²-2-bromoethyl pyrrolidinyl diazen-1-ium-1,2-diolate 在 双氧水 、 二氯二氧化钼 、 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 4.0h， 生成 O²-{(R)-2-[(S)-4-amino-4-carboxybutanamido]-3-[(carboxymethyl)amino]-3-oxopropyl}sulfonylethylpyrrolidinyl diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Glutathione S-Transferase π-Activatable O²-(Sulfonylethyl Derived) Diazeniumdiolates Potently Suppress Melanoma in Vitro and in Vivo

  摘要：

  A group of glutathione S-transferase pi (GST pi) activatable O-2-(sulfonylethyl derived) diazeniumdiolates 5-12 were designed and synthesized. These compounds could be activated by GST pi to initiate the beta-elimination reaction, liberating an active vinyl sulfone-based GSH derivative and a diazeniumdiolate anion which subsequently releases NO in situ. The most active compound 6 released relatively high levels of NO and inhibited proliferation of melanoma B16 cells, superior to a diazeniumdiolate-based anticancer agent JS-K (1). Importantly, 6 had 8-fold less inhibitory activity against normal epithelial JB6 Cl 30-7b cells. The inhibitory activity of 6 could be diminished by an NO scavenger or GST pi inhibitor. Furthermore, 6 induced nitration of mitochondrial tyrosine in B16 cells and inoculated B16 tumors in mice, which might be responsible for oxidation of protein leading to tumor suppression. Finally, 6 significantly retarded the B16 cells growth in a mouse xenograft model. These findings suggest that 6 may have a potential to treat melanoma.

  DOI：

  10.1021/acs.jmedchem.7b01178
• 作为产物：
  描述：

  sodium 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 、 三氟甲磺酸2-溴-乙酯 在 15-冠醚-5 作用下， 以 四氢呋喃 为溶剂， 以58%的产率得到O²-2-bromoethyl pyrrolidinyl diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Glutathione S-Transferase π-Activatable O²-(Sulfonylethyl Derived) Diazeniumdiolates Potently Suppress Melanoma in Vitro and in Vivo

  摘要：

  A group of glutathione S-transferase pi (GST pi) activatable O-2-(sulfonylethyl derived) diazeniumdiolates 5-12 were designed and synthesized. These compounds could be activated by GST pi to initiate the beta-elimination reaction, liberating an active vinyl sulfone-based GSH derivative and a diazeniumdiolate anion which subsequently releases NO in situ. The most active compound 6 released relatively high levels of NO and inhibited proliferation of melanoma B16 cells, superior to a diazeniumdiolate-based anticancer agent JS-K (1). Importantly, 6 had 8-fold less inhibitory activity against normal epithelial JB6 Cl 30-7b cells. The inhibitory activity of 6 could be diminished by an NO scavenger or GST pi inhibitor. Furthermore, 6 induced nitration of mitochondrial tyrosine in B16 cells and inoculated B16 tumors in mice, which might be responsible for oxidation of protein leading to tumor suppression. Finally, 6 significantly retarded the B16 cells growth in a mouse xenograft model. These findings suggest that 6 may have a potential to treat melanoma.

  DOI：

  10.1021/acs.jmedchem.7b01178

文献信息

• Improved synthesis of V-PYRRO/NO, a liver-selective nitric oxide prodrug, and analogues
  作者：Sam Y. Hong、Joseph E. Saavedra、Larry K. Keefer、Harinath Chakrapani

  DOI：10.1016/j.tetlet.2009.02.103

  日期：2009.5

  The reported synthesis of O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate(V-PYRRO/NO), a hepatoprotective agent, was cumbersome and limited by a poor overall yield of 4% from sodium 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (PYRRO/No). We report an improved synthesis of V-PYRRO/NO in two steps with a significantly higher overall yield of 40% from PYRRO/NO. Using this protocol, a number of structural analogues of V-PYRRO/NO were prepared in good yields. Published by Elsevier Ltd.
• Glutathione <i>S</i>-Transferase π-Activatable <i>O</i>²-(Sulfonylethyl Derived) Diazeniumdiolates Potently Suppress Melanoma in Vitro and in Vivo
  作者：Zhangjian Huang、Jianbing Wu、Yu Zou、Haoliang Yuan、Yinqiu Zhang、Yue Fei、Atul Bhardwaj、Jatinder Kaur、Edward E. Knaus、Yihua Zhang

  DOI：10.1021/acs.jmedchem.7b01178

  日期：2018.3.8

  A group of glutathione S-transferase pi (GST pi) activatable O-2-(sulfonylethyl derived) diazeniumdiolates 5-12 were designed and synthesized. These compounds could be activated by GST pi to initiate the beta-elimination reaction, liberating an active vinyl sulfone-based GSH derivative and a diazeniumdiolate anion which subsequently releases NO in situ. The most active compound 6 released relatively high levels of NO and inhibited proliferation of melanoma B16 cells, superior to a diazeniumdiolate-based anticancer agent JS-K (1). Importantly, 6 had 8-fold less inhibitory activity against normal epithelial JB6 Cl 30-7b cells. The inhibitory activity of 6 could be diminished by an NO scavenger or GST pi inhibitor. Furthermore, 6 induced nitration of mitochondrial tyrosine in B16 cells and inoculated B16 tumors in mice, which might be responsible for oxidation of protein leading to tumor suppression. Finally, 6 significantly retarded the B16 cells growth in a mouse xenograft model. These findings suggest that 6 may have a potential to treat melanoma.