phenyl (5-(trifluoromethyl)thiazol-2-yl)carbamate | 1245738-93-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: phenyl (5-(trifluoromethyl)thiazol-2-yl)carbamate
• 英文别名: phenyl [5-(trifluoromethyl)-1,3-thiazol-2-yl]carbamate；phenyl N-[5-(trifluoromethyl)-1,3-thiazol-2-yl]carbamate
• CAS: 1245738-93-5
• 化学式: C₁₁H₇F₃N₂O₂S
• 分子量: 288.25
• InChiKey: BRFTUINXFNCIOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3-氯-4-甲基苯基)哌嗪 、 phenyl (5-(trifluoromethyl)thiazol-2-yl)carbamate 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以16%的产率得到4-(3-chloro-4-methylphenyl)-N-(5-(trifluoromethyl)thiazol-2-yl)piperazine-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：

  5-(三氟甲基)噻唑-2-胺 、 氯甲酸苯酯 在 吡啶 作用下， 反应 5.0h， 以79%的产率得到phenyl (5-(trifluoromethyl)thiazol-2-yl)carbamate
  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

• Heterocyclic Compounds as CCR2 Antagonists
  申请人：Bower Justin Fairfield

  公开号：US20120264762A1

  公开（公告）日：2012-10-18

  Compounds of formula (I) Q-L-W—C(═X)—Z—P wherein Q is an amine of the formula —N(R 1 )(R 2 ); L is an alkyl or heterocyclyl-alkyl linker; W is a 6- or 7-membered aliphatic ring comprising ring atoms Y 1 and Y 2 which are linked to groups L and C(X) respectively and Y 1 and Y 2 are independently selected from N and C; X is O, N, N—CN or S; Z is NR 3 ; P is an optionally substituted monocyclic or bicyclic aryl or heteroaryl group; and pharmaceutically acceptable salts or solvates thereof, are useful in the treatment of C—C chemokine mediated conditions.

  化合物的式子为(I)Q-L-W—C(═X)—Z—P，其中Q是公式—N(R1)(R2)的胺基；L是烷基或杂环烷基-烷基连接物；W是一个6-或7-成员的脂肪环，包括环原子Y1和Y2，它们分别与基团L和C(X)相连，Y1和Y2独立地选自N和C；X是O、N、N—CN或S；Z是NR3；P是一个可选择取代的单环或双环芳基或杂芳基基团；以及其药学上可接受的盐或溶剂，用于治疗C-C趋化因子介导的疾病。