S-2-(nitrooxy)ethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate | 1170733-41-1

• 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: S-2-(nitrooxy)ethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate
• 英文别名: S-(2-nitrooxyethyl) N-methyl-N-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]carbamothioate
• CAS: 1170733-41-1
• 化学式: C₂₀H₂₁F₃N₂O₅S
• 分子量: 458.458
• InChiKey: OSRVULQFFKJSQU-UHFFFAOYSA-N

物化性质

• 沸点：
  550.5±60.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  S-2-(nitrooxy)ethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate 在 水 作用下， 反应 3.17h， 生成 氟西汀
  参考文献：
  名称：

  Chimeric Nitrate Esters and Use of the Same in a Treatment for Depression

  摘要：

  混合硝酸酯类化合物及其在治疗抑郁症中的应用被披露。这些混合硝酸酯类化合物也在治疗与衰老相关的抑郁症和共病中具有用途。

  公开号：

  US20090182011A1
• 作为产物：
  描述：

  盐酸氟西汀 在 silver nitrate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 50.25h， 生成 S-2-(nitrooxy)ethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate
  参考文献：
  名称：

  NO-SSRIs: Nitric Oxide Chimera Drugs Incorporating a Selective Serotonin Reuptake Inhibitor

  摘要：

  Hybrid nitrate drugs have been reported to provide NO bioactivity to ameliorate side effects or to provide ancillary therapeutic activity. Hybrid nitrate selective serotonin reuptake inhibitors (NO-SSRIs) were prepared to improve the therapeutic profile of this drug class. A synthetic strategy for use of a thiocarbamate linker was developed, which in the case of NO-fluoxetine facilitated hydrolysis to fluoxetine at pH 7.4 within 7 h. In cell culture, NO-SSRIs were weak inhibitors of the serotonin transporter; however, in the forced swimming task (FST) in rats, NO-fluoxetine demonstrated classical antidepressant activity. Comparison of NO-fluoxetine, with fluoxetine, and an NO-chimera nitrate developed for Alzheimer's disease (GT-1061) were made in the step through passive avoidance (STPA) test of learning and memory in rats treated with scopolamine as an amnesic agent. Fluoxetine was inactive, whereas NO-fluoxetine and GT-1061 both restored long-term memory. GT-1061 also produced antidepressant behavior in FST. These data support the potential for NO-SSRIs to overcome the lag in onset of therapeutic action and provide cotherapy of neuropathologies concomitant with depression.

  DOI：

  10.1021/ml2000033

文献信息

• Chimeric Nitrate Esters and Use of the Same in a Treatment for Depression
  申请人：Thatcher Gregory R.J.

  公开号：US20090182011A1

  公开（公告）日：2009-07-16

  Chimeric nitrate esters and their use in the treatment of depression are disclosed. The chimeric nitrate esters also are useful in the treatment of depression and comorbidity associated with aging.

  混合硝酸酯类化合物及其在治疗抑郁症中的应用被披露。这些混合硝酸酯类化合物也在治疗与衰老相关的抑郁症和共病中具有用途。
• NO-SSRIs: Nitric Oxide Chimera Drugs Incorporating a Selective Serotonin Reuptake Inhibitor
  作者：Samer Abdul-Hay、Isaac T. Schiefer、R. Esala P. Chandrasena、Min Li、Ramy Abdelhamid、Yue-Ting Wang、Ehsan Tavassoli、Bradley Michalsen、Rezene T. Asghodom、Jia Luo、Gregory R. J. Thatcher

  DOI：10.1021/ml2000033

  日期：2011.9.8

  Hybrid nitrate drugs have been reported to provide NO bioactivity to ameliorate side effects or to provide ancillary therapeutic activity. Hybrid nitrate selective serotonin reuptake inhibitors (NO-SSRIs) were prepared to improve the therapeutic profile of this drug class. A synthetic strategy for use of a thiocarbamate linker was developed, which in the case of NO-fluoxetine facilitated hydrolysis to fluoxetine at pH 7.4 within 7 h. In cell culture, NO-SSRIs were weak inhibitors of the serotonin transporter; however, in the forced swimming task (FST) in rats, NO-fluoxetine demonstrated classical antidepressant activity. Comparison of NO-fluoxetine, with fluoxetine, and an NO-chimera nitrate developed for Alzheimer's disease (GT-1061) were made in the step through passive avoidance (STPA) test of learning and memory in rats treated with scopolamine as an amnesic agent. Fluoxetine was inactive, whereas NO-fluoxetine and GT-1061 both restored long-term memory. GT-1061 also produced antidepressant behavior in FST. These data support the potential for NO-SSRIs to overcome the lag in onset of therapeutic action and provide cotherapy of neuropathologies concomitant with depression.