(5E)-5-[(2-氨基乙氧基)亚氨基]-5-[4-(三氟甲基)苯基]-1-戊醇 | 192876-02-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (5E)-5-[(2-氨基乙氧基)亚氨基]-5-[4-(三氟甲基)苯基]-1-戊醇
• 中文别名: 乙酮,2,2-二氟-1-(4-氟苯基)-2-(甲硫基)-(9CI)；氟伏沙明杂质G
• 英文名称: Demethyl Fluvoxamine
• 英文别名: desmethyl fluvoxamine；5-methoxy-4'-(trifluoromethyl)valerophenone-(E)-O-(2-aminoethyl)oxime maleate；Fluvoxamino Acid；(5E)-5-(2-aminoethoxyimino)-5-[4-(trifluoromethyl)phenyl]pentan-1-ol
• CAS: 192876-02-1
• 化学式: C₁₄H₁₉F₃N₂O₂
• 分子量: 304.312
• InChiKey: GCSLDHTZSDNYEC-CPNJWEJPSA-N

物化性质

• 熔点：
  74-76°C
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

氟伏沙明醇是氟伏沙明的已知人体代谢物。

Fluvoxamino alcohol is a known human metabolite of fluvoxamine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  马来酸氟伏沙明 在 reconstituted human liver microsomes glucose-6-phosphate dehydrogenase 、 Α-D-吡喃葡萄糖6-磷酸 、 nicotinamide adenine dinucleotide phosphate 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 (5E)-5-[(2-氨基乙氧基)亚氨基]-5-[4-(三氟甲基)苯基]-1-戊醇
  参考文献：
  名称：

  Identification of human cytochrome P450 enzymes involved in the major metabolic pathway of fluvoxamine

  摘要：

  The metabolism of fluvoxamine to fluvoxamino acid is known to involve a two-step oxidation process via an alcohol intermediate, fluvoxamino alcohol. The present study was carried out to identify the cytochrome P450 (CYP) enzyme(s) involved in the metabolism of fluvoxamine to fluvoxamino alcohol using human liver microsomes and cDNA-expressed human CYP enzymes. The mean Km and Vmax values for the formation of fluvoxamino alcohol from fluvoxamine in human liver microsomes were 76.3 mu M and 37.5 pmol min(-1) mg(-1) protein, respectively. The formation of fluvoxamino alcohol from fluvoxamine in pooled human liver microsomes was significantly inhibited by quinidine, a relatively specific CYP2D6 inhibitor, with a K-i value of 2.2 mu M, whereas other several relatively specific CYP inhibitors did not inhibit the formation of fluvoxamino alcohol. In addition, only CYP2D6 of several cDNA-expressed human CYP enzymes examined showed substantial activity for the formation of fluvoxamino alcohol. Furthermore, the formation of fluvoxamino acid from fluvoxamino alcohol is potently inhibited by 4-methylpyrazole in human liver cytosol. These data suggest that CYP2D6 is the only enzyme predominantly responsible for the first-step oxidation of fluvoxamine to fluvoxamino alcohol, and alcohol dehydrogenase is involved in the second-step oxidation of fluvoxamino alcohol to the corresponding carbolic acid.

  DOI：

  10.1080/00498250600718464

文献信息

• AN IMPROVED PROCESS FOR THE PREPARATION OF FLUVOXAMINE MALEATE
  申请人：ZCL CHEMICALS LIMITED

  公开号：US20160168080A1

  公开（公告）日：2016-06-16

  The present invention relates to an industrially feasible and economically viable process for the preparation of fluvoxamine maleate of formula I.

  本发明涉及一种工业上可行且经济可行的制备化合物I的氟伏沙明盐的过程。
• EP2981518B1
  申请人：——

  公开号：EP2981518B1

  公开（公告）日：2021-03-03
• US9783492B2
  申请人：——

  公开号：US9783492B2

  公开（公告）日：2017-10-10
• Identification of human cytochrome P450 enzymes involved in the major metabolic pathway of fluvoxamine
  作者：M. Miura、T. Ohkubo

  DOI：10.1080/00498250600718464

  日期：2007.2

  The metabolism of fluvoxamine to fluvoxamino acid is known to involve a two-step oxidation process via an alcohol intermediate, fluvoxamino alcohol. The present study was carried out to identify the cytochrome P450 (CYP) enzyme(s) involved in the metabolism of fluvoxamine to fluvoxamino alcohol using human liver microsomes and cDNA-expressed human CYP enzymes. The mean Km and Vmax values for the formation of fluvoxamino alcohol from fluvoxamine in human liver microsomes were 76.3 mu M and 37.5 pmol min(-1) mg(-1) protein, respectively. The formation of fluvoxamino alcohol from fluvoxamine in pooled human liver microsomes was significantly inhibited by quinidine, a relatively specific CYP2D6 inhibitor, with a K-i value of 2.2 mu M, whereas other several relatively specific CYP inhibitors did not inhibit the formation of fluvoxamino alcohol. In addition, only CYP2D6 of several cDNA-expressed human CYP enzymes examined showed substantial activity for the formation of fluvoxamino alcohol. Furthermore, the formation of fluvoxamino acid from fluvoxamino alcohol is potently inhibited by 4-methylpyrazole in human liver cytosol. These data suggest that CYP2D6 is the only enzyme predominantly responsible for the first-step oxidation of fluvoxamine to fluvoxamino alcohol, and alcohol dehydrogenase is involved in the second-step oxidation of fluvoxamino alcohol to the corresponding carbolic acid.