4-(4-chloro-3-methylphenoxy)piperidine | 367501-05-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(4-chloro-3-methylphenoxy)piperidine
• CAS: 367501-05-1
• 化学式: C₁₂H₁₆ClNO
• 分子量: 225.718
• InChiKey: XGUPBEQGBNKGGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-chloro-3-methylphenoxy)piperidine 、 phenyl (5-chlorothiazol-2-yl)carbamate 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以47%的产率得到4-(4-chloro-3-methylphenoxy)-N-(5-chlorothiazol-2-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254
• 作为产物：
  描述：

  4-氯-3-甲基苯酚 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.17h， 生成 4-(4-chloro-3-methylphenoxy)piperidine
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254

文献信息

• Chemical compounds
  申请人：——

  公开号：US20040102432A1

  公开（公告）日：2004-05-27

  The invention provides compounds of formula (I): as modulators of chemokine and H1 receptor activity. The compounds are especially useful in the treatment of asthma and rhinitis.

  该发明提供了化合物的公式（I）：作为趋化因子和H1受体活性的调节剂。这些化合物在哮喘和鼻炎的治疗中特别有用。
• Substituted bipiperidine intermediates and derivatives thereof
  申请人：AstraZeneca AB

  公开号：EP1493743A1

  公开（公告）日：2005-01-05

  A compound of formula (Xllla): wherein: L2 is hydrogen, tert-butoxycarbonyl or benzyl; t is 0 or 1; m and p are, independently, 0, 1 or 2; X is CH2, C(O), O, S, S(O), S(O)2 or NR37; provided that when m and p are both 1 then X is not CH2; and R1 has specified values.

  一种式(Xllla)化合物： 其中L2 是氢、叔丁氧基羰基或苄基；t 是 0 或 1；m 和 p 分别是 0、1 或 2；X 是 CH2、C(O)、O、S、S(O)、S(O)2 或 NR37；但当 m 和 p 均为 1 时，X 不是 CH2；R1 具有指定值。
• INTERMEDIATES FOR THE PREPARATION OF PIPERIDINE DERIVATIVES USEFUL AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1604982A1

  公开（公告）日：2005-12-14

  The invention provides a compound of formula (X) or (XVIII): wherein: R1 is optionally substituted aryl or optionally substituted heterocyclyl; and R2 is hydrogen or C1-6 alkyl; said compounds can be used for preparing modulators of chemokine (especially CCR3) activity.

  本发明提供了一种式 (X) 或 (XVIII) 的化合物： 其中R1是任选取代的芳基或任选取代的杂环基；R2是氢或C1-6烷基；所述化合物可用于制备趋化因子（尤其是CCR3）活性调节剂。
• [1,4']-BIPIPERIDINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1274701B1

  公开（公告）日：2005-06-29
• CHEMICAL COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1322611A1

  公开（公告）日：2003-07-02