10-N-(8-hydroxyoctyl)-2-(trifluoromethyl)phenothiazine | 183899-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 10-N-(8-hydroxyoctyl)-2-(trifluoromethyl)phenothiazine
• 英文别名: 8-[2-(trifluoromethyl)phenothiazin-10-yl]octan-1-ol
• CAS: 183899-74-3
• 化学式: C₂₁H₂₄F₃NOS
• 分子量: 395.489
• InChiKey: WIXAZFZHHJNPNX-UHFFFAOYSA-N

物化性质

• 沸点：
  498.9±45.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.64
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  23.47
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  10-N-(8-hydroxyoctyl)-2-(trifluoromethyl)phenothiazine 在 重铬酸吡啶 、 盐酸羟胺 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 (Z)-10-N-(7-oximinooctyl)-2-(trifluoromethyl)phenothiazine
  参考文献：
  名称：

  N-Oxygenation of Primary Amines and Hydroxylamines and Retroreduction of Hydroxylamines by Adult Human Liver Microsomes and Adult Human Flavin-Containing Monooxygenase 3

  摘要：

  Adult human liver microsomes catalyze the NADPH-dependent N-oxygenation of 10-N-(n-octylamino)-2-(trifluoromethyl)phenothiazine to the corresponding oximes through the intermediacy of the hydroxylamine. In the presence of adult human liver microsomes, the primary amine is stereoselectively converted to the cis-oxime, but addition of the alternative competitive substrate hydroxylamine hydrochloride apparently decreases the amount of aliphatic hydroxylamine retroreduction because an increase in oxime formation was observed. In the presence of hydroxylamine hydrochloride, however, the oxime product recovered was formed with very low stereoselectivity. Studies on the biochemical mechanism of oxime formation suggested that cis-oxime formation in the presence of adult human liver microsomes was largely dependent on the human flavin-containing monooxygenase (form 3). This conclusion is based on the effects of incubation conditions on product formation when compared to results observed in the presence of cDNA-expressed human FMO3. The retroreduction of the intermediate hydroxylamine was dependent on NADPH but was not catalyzed by human flavin-containing monooxygenase (form 3) or any one of seven prominent cytochromes P-450 that have been well-characterized in the human liver microsomes examined. The results suggest that aliphatic primary amines are efficiently sequentially N-oxygenated in the presence of human liver microsomes to hydroxylamines and then to oximes mainly by the human flavin-containing monooxygenase. Retroreduction of the intermediate hydroxylamine is apparently facilitated by a novel but as yet poorly characterized enzyme system that does not employ any of the currently known well-characterized cytochrome P-450 enzymes present in adult human liver microsomes.

  DOI：

  10.1021/tx9600614
• 作为产物：
  描述：

  8-溴-1-辛醇 、 2-三氟甲基吩噻嗪 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 以55%的产率得到10-N-(8-hydroxyoctyl)-2-(trifluoromethyl)phenothiazine
  参考文献：
  名称：

  N-Oxygenation of Primary Amines and Hydroxylamines and Retroreduction of Hydroxylamines by Adult Human Liver Microsomes and Adult Human Flavin-Containing Monooxygenase 3

  摘要：

  Adult human liver microsomes catalyze the NADPH-dependent N-oxygenation of 10-N-(n-octylamino)-2-(trifluoromethyl)phenothiazine to the corresponding oximes through the intermediacy of the hydroxylamine. In the presence of adult human liver microsomes, the primary amine is stereoselectively converted to the cis-oxime, but addition of the alternative competitive substrate hydroxylamine hydrochloride apparently decreases the amount of aliphatic hydroxylamine retroreduction because an increase in oxime formation was observed. In the presence of hydroxylamine hydrochloride, however, the oxime product recovered was formed with very low stereoselectivity. Studies on the biochemical mechanism of oxime formation suggested that cis-oxime formation in the presence of adult human liver microsomes was largely dependent on the human flavin-containing monooxygenase (form 3). This conclusion is based on the effects of incubation conditions on product formation when compared to results observed in the presence of cDNA-expressed human FMO3. The retroreduction of the intermediate hydroxylamine was dependent on NADPH but was not catalyzed by human flavin-containing monooxygenase (form 3) or any one of seven prominent cytochromes P-450 that have been well-characterized in the human liver microsomes examined. The results suggest that aliphatic primary amines are efficiently sequentially N-oxygenated in the presence of human liver microsomes to hydroxylamines and then to oximes mainly by the human flavin-containing monooxygenase. Retroreduction of the intermediate hydroxylamine is apparently facilitated by a novel but as yet poorly characterized enzyme system that does not employ any of the currently known well-characterized cytochrome P-450 enzymes present in adult human liver microsomes.

  DOI：

  10.1021/tx9600614