(S)-2-[3-chloro-1-(naphthalen-1-yloxy)-propyl]-thiophene | 164071-61-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-2-[3-chloro-1-(naphthalen-1-yloxy)-propyl]-thiophene
• 英文别名: S-3-chloro-1-(2-thienyl)-1-(1-naphthalenyloxy)propane；(S)-2-(3-Chloro-1-(naphthalen-1-yloxy)propyl)thiophene；2-[(1S)-3-chloro-1-naphthalen-1-yloxypropyl]thiophene
• CAS: 164071-61-8
• 化学式: C₁₇H₁₅ClOS
• 分子量: 302.824
• InChiKey: HFXILOQSAVSOQT-INIZCTEOSA-N

物化性质

• 沸点：
  464.9±30.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  37.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-[3-chloro-1-(naphthalen-1-yloxy)-propyl]-thiophene 在 sodium iodide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 生成 度洛西汀
  参考文献：
  名称：

  Duloxetine (Cymbalta™), a dual inhibitor of serotonin and norepinephrine reuptake

  摘要：

  A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta(TM)) has proven to be effective in clinical trials for the treatment of depression. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.079
• 作为产物：
  描述：

  2-(3-氯丙酰基)噻吩 在 硼烷 、 三苯基膦 、 (S)-2-甲基-CBS-恶唑硼烷 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-[3-chloro-1-(naphthalen-1-yloxy)-propyl]-thiophene
  参考文献：
  名称：

  Duloxetine (Cymbalta™), a dual inhibitor of serotonin and norepinephrine reuptake

  摘要：

  A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta(TM)) has proven to be effective in clinical trials for the treatment of depression. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.079

文献信息

• An asymmetric synthesis of duloxetine hydrochloride, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled isotopomers
  作者：William J. Wheeler、Fengjiun Kuo

  DOI：10.1002/jlcr.2580360303

  日期：1995.3

  Two 14 C-isotopomers of duloxetine HCl (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride), a potent mixed serotonin/norepinephrine uptake inhibitor have been prepared by an asymmetric synthesis. The palladium catalyzed cross-coupling of 2-thienoyl chloride (3c) (or its [carbonyl- 14 C] isotopomer 3d) with vinyl tri-n-butyl-stannane, followed by addition of HCl afforded the

  盐酸度洛西汀 (S-(+)-N-methyl-3(1-naphthalenyloxy)-3(2-thiophene)propanamine hydrochloride) 的两种 14 C-同位素异构体，一种有效的混合血清素/去甲肾上腺素摄取抑制剂已通过不对称方法制备合成。钯催化 2-噻吩酰氯 (3c)（或其 [羰基- 14 C] 同位素异构体 3d）与乙烯基三正丁基锡烷的交叉偶联，然后加入 HCl，得到关键的前手性中间体氯酮（ 5a,b) 在适当的氧氮杂硼烷催化剂（14a 或 b）存在下用硼烷进行手性还原，得到 5-氯代醇（7a）及其 14 C 标记的对应物 7b 或类似的 R-氯代醇（6）。通过与 NaI/丙酮反应活化 7a,b，然后相应的碘醇与甲胺反应产生倒数第二个氨基醇 (8a,b)。与 NaH 形成醇盐，然后与 1-氟萘反应产生度洛西汀或其 14 C-标记的同位素异构体 9。或者，6
• 盐酸度洛西汀杂质，其制备及分析方法
  申请人：浙江晖石药业有限公司

  公开号：CN113929657A

  公开（公告）日：2022-01-14

  本发明提供了盐酸度洛西汀杂质，其制备及分析方法，可以更好地控制盐酸度洛西汀的质量。两个杂质的结构式如下：
• Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression
  作者：John R. Cashman、Senait Ghirmai

  DOI：10.1016/j.bmc.2009.08.025

  日期：2009.10

  Compounds possessing more than one functional activity incorporated into the same molecule may have advantages in treating complex disease states. Balanced serotonin/norepinephrine reuptake inhibitors (SNRIs) (i.e., (R)- and (S)-norduloxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) showed moderately potent serotonin reuptake inhibition (IC(50) values of 442 and 404 nM, respectively) but low reuptake inhibition of norepinephrine (IC(50) values of 2097 and 2190 nM, respectively) in vitro. The dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) also inhibited PDE4D2 (i.e., K(i) values of 23 and 45 nM, respectively). Due to their synergistic functional activity, SNRI/PDE4 inhibitors may be effective in treating diseases such as depression. (C) 2009 Elsevier Ltd. All rights reserved.