1-N-(tert-butoxycarbonyl)-4-N-(5,6-dichloropyridin-3-yl)piperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-N-(tert-butoxycarbonyl)-4-N-(5,6-dichloropyridin-3-yl)piperazine
• 英文别名: Tert-butyl 4-(5,6-dichloropyridin-3-yl)piperazine-1-carboxylate；tert-butyl 4-(5,6-dichloropyridin-3-yl)piperazine-1-carboxylate
• 化学式: C₁₄H₁₉Cl₂N₃O₂
• 分子量: 332.23
• InChiKey: LBJIMIPDXNTNEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-N-(tert-butoxycarbonyl)-4-N-(5,6-dichloropyridin-3-yl)piperazine 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 121.0h， 生成 2-(4-(5,6-dichloropyridin-3-yl)piperazin-1-yl)-6-methyl-3H-imidazo[4,5-b]pyridine
  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：

  5-溴-2,3-二氯吡啶 、 N-Boc-哌嗪 在 tris(dibenzylideneacetone)dipalladium (0) 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以87%的产率得到1-N-(tert-butoxycarbonyl)-4-N-(5,6-dichloropyridin-3-yl)piperazine
  参考文献：
  名称：

  Selective Amination of Polyhalopyridines Catalyzed by a Palladium−Xantphos Complex

  摘要：

  Amination of 5-bromo-2-chloropyridine (1a) catalyzed by a palladium-Xantphos complex predominately gives 5-amino-2-chloropyridine product 3a in 96% isolated yield and excellent chemoselectivity (3a/4a = 97:3). Amination of 2,5-dibromopyridine (11) under the same conditions exclusively affords 2-amino-5-bromopyridine 4a.

  DOI：

  10.1021/ol0357696

文献信息

• Selective Amination of Polyhalopyridines Catalyzed by a Palladium−Xantphos Complex
  作者：Jianguo Ji、Tao Li、William H. Bunnelle

  DOI：10.1021/ol0357696

  日期：2003.11.1

  Amination of 5-bromo-2-chloropyridine (1a) catalyzed by a palladium-Xantphos complex predominately gives 5-amino-2-chloropyridine product 3a in 96% isolated yield and excellent chemoselectivity (3a/4a = 97:3). Amination of 2,5-dibromopyridine (11) under the same conditions exclusively affords 2-amino-5-bromopyridine 4a.
• Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
  作者：William Nguyen、Jonathan Jacobson、Kate E. Jarman、Timothy R. Blackmore、Helene Jousset Sabroux、Sharon R. Lewin、Damian F. Purcell、Brad E. Sleebs

  DOI：10.1016/j.ejmech.2020.112254

  日期：2020.6

  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.