(-)-(S)-Flosequinan | 154504-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (-)-(S)-Flosequinan
• 英文别名: (-)-Flosequinan；4(1H)-Quinolinone, 7-fluoro-1-methyl-3-[(S)-methylsulfinyl]-；7-fluoro-1-methyl-3-[(S)-methylsulfinyl]quinolin-4-one
• CAS: 154504-94-6
• 化学式: C₁₁H₁₀FNO₂S
• 分子量: 239.27
• InChiKey: UYGONJYYUKVHDD-INIZCTEOSA-N

物化性质

• 沸点：
  423.1±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (-)-(S)-Flosequinan 在 rat liver microsomes 作用下， 反应 0.17h， 生成 7-氟-1-甲基-3-甲基磺酰基喹啉-4-酮
  参考文献：
  名称：

  Stereoselective S-oxidation and reduction of flosequinan in rat

  摘要：

  1. The stereoselective S-oxidation and reduction pathways of flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone] in rat were investigated in vitro.2. Cytosol from both the liver and kidney catalysed the reduction of R(+)-flosequinan (R-FSO) and S(-)-flosequinan (S-FSO) to flosequinan sulphide (FS, 7-fluoro-1-methyl-3-methylthio-4-quinolone). Flosequinan sulphone (FSO2, 7-fluoro-1-methyl-3-methyl-sulphonyl-4-quinolone) was not reduced to R-FSO or S-FSO.3. Liver microsomes catalysed four different S-oxidation pathways in the presence of NADPH, namely oxidation of FS to R-FSO and S-FSO and from R-FSO and S-FSO to FSO2. The formation of R-FSO and S-FSO from FS each exhibited a biphasic kinetic pattern, indicating that at least two distinct enzymes were involved. The pathway from FS to R-FSO appeared mainly catalysed by flavin-containing monooxygenases (FMO).4. S-oxidation of FS to R-FSO was more rapid than that of FS to S-FSO. S-oxidation of FS to either R-FSO or S-FSO in liver microsomes was more rapid than that of either R-FSO or S-FSO to FSO2.5. Microsomes from both the kidney and lung catalysed the stereoselective S-oxidation of FS to R-FSO, and FMO was likely to have participated in these reactions.

  DOI：

  10.1080/004982599238263
• 作为产物：
  描述：

  7-fluoro-3-methylthio-4-quinolone 在 盐酸 、 potassium carbonate 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 氯仿 、 丁酮 为溶剂， 反应 44.0h， 生成 (-)-(S)-Flosequinan
  参考文献：
  名称：

  Synthesis and Absolute Configuration of the Enantiomers of 7-Fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolinone (Flosequinan).

  摘要：

  7-氟-1-甲基-3-(甲基亚磺酰基)-4(1H)-喹啉酮的对映异构体（±）-1，一种治疗心力衰竭的新药，是从喹啉的光学活性（R）-α-甲基苄胺衍生物合成的。关键中间体（R）-α-甲基苄胺衍生物是通过非对映异构体分离制备的。根据合成前体（4a）的X射线晶体学分析，确定了（+）-1的构型。发现绝对构型为（R）-（+）-1和（S）-（-）-1。

  DOI：

  10.1248/cpb.42.2157

文献信息

• Stereospecific enrichment of heterocyclic enantiomers
  申请人：R.T. Alamo Adventures I, LLC

  公开号：US20030120075A1

  公开（公告）日：2003-06-26

  The present invention describes methods for the stereoselective synthesis of heterocyclic enantiomers. The methods of the present invention incorporate the stereo-preferred oxidation of quinolone thiomethyl intermediates by optically active camphor based oxaziridines to provide R(+) or S(−) quinolone methylsulfinyl derivatives.

  本发明描述了手性杂环对映体的立体选择性合成方法。本发明的方法包括利用光学活性莰烯基氧杂环化合物对喹啉硫甲基中间体进行立体选择性氧化，从而提供R（+）或S（−）喹啉甲基亚磺酰衍生物。
• US6649764B2
  申请人：——

  公开号：US6649764B2

  公开（公告）日：2003-11-18
• US7084275B2
  申请人：——

  公开号：US7084275B2

  公开（公告）日：2006-08-01
• Stereoselective S-oxidation and reduction of flosequinan in rat
  作者：E. KASHIYAMA、T. YOKOI、M. ODOMI、T. KAMATAKI

  DOI：10.1080/004982599238263

  日期：1999.1

  1. The stereoselective S-oxidation and reduction pathways of flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone] in rat were investigated in vitro.2. Cytosol from both the liver and kidney catalysed the reduction of R(+)-flosequinan (R-FSO) and S(-)-flosequinan (S-FSO) to flosequinan sulphide (FS, 7-fluoro-1-methyl-3-methylthio-4-quinolone). Flosequinan sulphone (FSO2, 7-fluoro-1-methyl-3-methyl-sulphonyl-4-quinolone) was not reduced to R-FSO or S-FSO.3. Liver microsomes catalysed four different S-oxidation pathways in the presence of NADPH, namely oxidation of FS to R-FSO and S-FSO and from R-FSO and S-FSO to FSO2. The formation of R-FSO and S-FSO from FS each exhibited a biphasic kinetic pattern, indicating that at least two distinct enzymes were involved. The pathway from FS to R-FSO appeared mainly catalysed by flavin-containing monooxygenases (FMO).4. S-oxidation of FS to R-FSO was more rapid than that of FS to S-FSO. S-oxidation of FS to either R-FSO or S-FSO in liver microsomes was more rapid than that of either R-FSO or S-FSO to FSO2.5. Microsomes from both the kidney and lung catalysed the stereoselective S-oxidation of FS to R-FSO, and FMO was likely to have participated in these reactions.
• Synthesis and Absolute Configuration of the Enantiomers of 7-Fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolinone (Flosequinan).
  作者：Seiji MORITA、Kenji OHTSUBO、Jun MATSUBARA、Tadaaki OHTANI、Minoru UCHIDA、Masaru KIDO、Takefumi SHIMIZU

  DOI：10.1248/cpb.42.2157

  日期：——

  The enantiomers of 7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolinone [(±)-1, flosequinan], a new drug for the treatment of heart failure, were synthesized from the optically active (R)-α-methylbenzylamine derivatives of quinoline. The key intermediates, (R)-α-methylbenzylamine derivatives, were prepared by diastereomeric separation. The configuration of (+)-1 was assigned on the basis of an X-ray crystallographic analysis of the synthetic precursor (4a). The absolute configuration was found to be (R)-(+)-1 and (S)-(-)-1.

  7-氟-1-甲基-3-(甲基亚磺酰基)-4(1H)-喹啉酮的对映异构体（±）-1，一种治疗心力衰竭的新药，是从喹啉的光学活性（R）-α-甲基苄胺衍生物合成的。关键中间体（R）-α-甲基苄胺衍生物是通过非对映异构体分离制备的。根据合成前体（4a）的X射线晶体学分析，确定了（+）-1的构型。发现绝对构型为（R）-（+）-1和（S）-（-）-1。