N-acetylparoxetine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-acetylparoxetine
• 英文别名: 1-[(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidin-1-yl]ethanone
• 化学式: C₂₁H₂₂FNO₄
• 分子量: 371.408
• InChiKey: UQXZOFZRYGCMMY-LPHOPBHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  乙酸酐 、 帕罗西汀 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以98%的产率得到N-acetylparoxetine
  参考文献：
  名称：

  Selective serotonin reuptake inhibitors—A new modality for the treatment of lymphoma/leukaemia?

  摘要：

  Selective serotonin reuptake inhibitors (SSRIs) have recently been reported to specifically kill malignant cells of B-lymphoid origin, i.e., cells derived from Burkitt lymphoma. Accordingly, SSRIs have been proposed as lead compounds in the development of new approaches to the treatment of lymphoma/leukaemia. Here we attempted to dissect the underlying signaling pathways by comparing susceptible and resistant cell lines. However, we found that all cell lines investigated underwent apoptotic cell death when exposed to SSRI concentrations exceeding 10 mu M regardless of whether the cell lines were derived from B- (e.g., Namalwa, Ramos, Daudi, RL7), T-lymphoid tumors (e.g., Molt-4, Jurkat, CCRF-CEM) or other sources. The structure-activity relationship readily distinguished the pro-apoptotic and growth inhibitory effect of SSRIs from their eponymous action (blockage of the serotonin transporter): acetylation of the SSRIs fluvoxamine and paroxetine abrogated the ability of these compounds to inhibit 5HT-uptake, but did not impair their cytotoxic action. Based on these data we conclude that (i) SSRIs inhibit growth of transformed cells, but that (h) this effect is neither specific for malignant cells nor specific for any particular cellular subset. (iii) The pro-apoptotic effect of SSRIs (at mu M concentrations) is unrelated to their principal pharmacological action, i.e., inhibition of serotonin uptake (at nM concentrations). SSRIs or improved versions thereof are therefore unlikely to represent useful lead compounds for inducing apoptosis in B-cell derived tumors: the underlying mechanism is not confined to any specific cell lineage. (C) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.07.017

文献信息

• Structural differences between paroxetine and femoxetine responsible for differential inhibition of Staphylococcus aureus efflux pumps
  作者：Peng Wei、Glenn W. Kaatz、Robert J. Kerns

  DOI：10.1016/j.bmcl.2004.04.018

  日期：2004.6

  In this study the chemical modification of paroxetine was employed to determine which structural differences between the paroxetine-like and femoxetine-like selective serotonin reuptake inhibitors is responsible for the differential potency of these agents in the inhibition of Staphylococcus aureus multidrug efflux pump systems. (C) 2004 Elsevier Ltd. All rights reserved.
• Selective serotonin reuptake inhibitors—A new modality for the treatment of lymphoma/leukaemia?
  作者：Christian Schuster、Nora Fernbach、Uwe Rix、Giulio Superti-Furga、Marion Holy、Michael Freissmuth、Harald H. Sitte、Veronika Sexl

  DOI：10.1016/j.bcp.2007.07.017

  日期：2007.11

  Selective serotonin reuptake inhibitors (SSRIs) have recently been reported to specifically kill malignant cells of B-lymphoid origin, i.e., cells derived from Burkitt lymphoma. Accordingly, SSRIs have been proposed as lead compounds in the development of new approaches to the treatment of lymphoma/leukaemia. Here we attempted to dissect the underlying signaling pathways by comparing susceptible and resistant cell lines. However, we found that all cell lines investigated underwent apoptotic cell death when exposed to SSRI concentrations exceeding 10 mu M regardless of whether the cell lines were derived from B- (e.g., Namalwa, Ramos, Daudi, RL7), T-lymphoid tumors (e.g., Molt-4, Jurkat, CCRF-CEM) or other sources. The structure-activity relationship readily distinguished the pro-apoptotic and growth inhibitory effect of SSRIs from their eponymous action (blockage of the serotonin transporter): acetylation of the SSRIs fluvoxamine and paroxetine abrogated the ability of these compounds to inhibit 5HT-uptake, but did not impair their cytotoxic action. Based on these data we conclude that (i) SSRIs inhibit growth of transformed cells, but that (h) this effect is neither specific for malignant cells nor specific for any particular cellular subset. (iii) The pro-apoptotic effect of SSRIs (at mu M concentrations) is unrelated to their principal pharmacological action, i.e., inhibition of serotonin uptake (at nM concentrations). SSRIs or improved versions thereof are therefore unlikely to represent useful lead compounds for inducing apoptosis in B-cell derived tumors: the underlying mechanism is not confined to any specific cell lineage. (C) 2007 Elsevier Inc. All rights reserved.