4-[(1S)-3-(甲基氨基)-1-(2-噻吩基)丙氧基]-1-萘酚 | 662149-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-[(1S)-3-(甲基氨基)-1-(2-噻吩基)丙氧基]-1-萘酚
• 中文别名: 度洛西汀杂质
• 英文名称: (S)-3-(4-hydroxynaphthalen-1-yl)-N-methyl-3-(thiophen-2-yl)propan-1-amine
• 英文别名: 4-Hydroxy Duloxetine；4-[(1S)-3-(methylamino)-1-thiophen-2-ylpropoxy]naphthalen-1-ol
• CAS: 662149-13-5
• 化学式: C₁₈H₁₉NO₂S
• 分子量: 313.42
• InChiKey: DRRXQCXSBONKPD-KRWDZBQOSA-N

物化性质

• 熔点：
  140-143°C
• 沸点：
  516.6±50.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（非常轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  69.7
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

4-羟基度洛西汀已知的人类代谢物包括 (2S,3S,4S,5R,6S)-3,4,5-三羟基-6-[4-[(1S)-3-(甲基铵基)-1-噻吩-2-基丙氧基]萘-1-基]氧代氧杂环己烷-2-羧酸盐。

4-Hydroxyduloxetine has known human metabolites that include (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-[4-[(1S)-3-(methylazaniumyl)-1-thiophen-2-ylpropoxy]naphthalen-1-yl]oxyoxane-2-carboxylate.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  4-[(1S)-3-(甲基氨基)-1-(2-噻吩基)丙氧基]-1-萘酚 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 4-Hydroxy-Duloxetine Glucuronide
  参考文献：
  名称：

  Synthesis and biological activity of some known and putative duloxetine metabolites

  摘要：

  Several putative phase I duloxetine metabolites, 4-hydroxy-, 5-hydroxy-, 6-hydroxy-, 5-hydroxy-6-methoxy-, 6-hydroxy5-methoxy-, 5,6-dihydroxy-, and 4,6-dihydroxyduloxetine were synthesized, and their phase II metabolite as glucuronide or sulfate conjugates were also synthesized. Their in vitro binding activities were compared to that of parent compound duloxetine. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.066
• 作为产物：
  描述：

  1,4-二羟基萘 在 哌啶 、 吡啶 、 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 1,4-双(二苯基膦)丁烷 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 29.5h， 生成 4-[(1S)-3-(甲基氨基)-1-(2-噻吩基)丙氧基]-1-萘酚
  参考文献：
  名称：

  Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory

  摘要：

  The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously.

  DOI：

  10.1016/j.chempr.2018.02.002

文献信息

• Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory
  作者：Tomasz Klucznik、Barbara Mikulak-Klucznik、Michael P. McCormack、Heather Lima、Sara Szymkuć、Manishabrata Bhowmick、Karol Molga、Yubai Zhou、Lindsey Rickershauser、Ewa P. Gajewska、Alexei Toutchkine、Piotr Dittwald、Michał P. Startek、Gregory J. Kirkovits、Rafał Roszak、Ariel Adamski、Bianka Sieredzińska、Milan Mrksich、Sarah L.J. Trice、Bartosz A. Grzybowski

  DOI：10.1016/j.chempr.2018.02.002

  日期：2018.3

  The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously.
• Synthesis and biological activity of some known and putative duloxetine metabolites
  作者：F. Kuo、T.A. Gillespie、P. Kulanthaivel、R.J. Lantz、T.W. Ma、D.L. Nelson、P.G. Threlkeld、W.J. Wheeler、P. Yi、M. Zmijewski

  DOI：10.1016/j.bmcl.2004.04.066

  日期：2004.7

  Several putative phase I duloxetine metabolites, 4-hydroxy-, 5-hydroxy-, 6-hydroxy-, 5-hydroxy-6-methoxy-, 6-hydroxy5-methoxy-, 5,6-dihydroxy-, and 4,6-dihydroxyduloxetine were synthesized, and their phase II metabolite as glucuronide or sulfate conjugates were also synthesized. Their in vitro binding activities were compared to that of parent compound duloxetine. (C) 2004 Elsevier Ltd. All rights reserved.