4-(3,5-dichlorophenoxy)butanoic acid | 87411-28-7

• 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: 4-(3,5-dichlorophenoxy)butanoic acid
• 英文别名: Butanoic acid, 4-(3,5-dichlorophenoxy)-
• CAS: 87411-28-7
• 化学式: C₁₀H₁₀Cl₂O₃
• 分子量: 249.094
• InChiKey: RDMMATAFNXXIGK-UHFFFAOYSA-N

物化性质

• 沸点：
  413.1±35.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3,5-dichlorophenoxy)butanoic acid 、 2-(3-aminopropenyl)-5-(6-aminopurin-9-yl)tetrahydrofuran-3,4-diol 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 、 溴乙腈 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 生成 N-{(E)-3-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]prop-2-enyl}butyramide
  参考文献：
  名称：

  使用红色安全捕捉链接器的裸眼珠属性估计

  摘要：

  将接头分子连接到用作有机合成不溶性载体的聚合物珠粒上是一种常见的要求。在加载选定的构建块之前确定这些连接分子的固定对于后续转化至关重要。因此，链接器附件的控制是一项中心任务。由于连接体的分子体不掺入最终分子中，因此它们通常可以被替换或修饰，而不会影响最终释放的产物的结构。因此，寻找已建立的连接分子的有色替代物似乎很简单。通过使用彩色接头，可以对珠子进行目视检查，从而在连接后快速评估属性并监测合成过程中的损失。这个非常简单的估计没有经过验证的加载确定，但它是直接和非破坏性反应控制的有用元素，具有普遍适用性。在这里，我们提出了一种红色偶氮染料作为 Kenner 安全捕获接头的替代品。

  DOI：

  10.1071/ch04262
• 作为产物：
  描述：

  3,5-二氯苯酚 在 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 4-(3,5-dichlorophenoxy)butanoic acid
  参考文献：
  名称：

  Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models

  摘要：

  The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.

  DOI：

  10.1021/acs.jmedchem.9b00462

文献信息

• Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV
  作者：Charlotta Sundin、Michael Saleeb、Sara Spjut、Liena Qin、Mikael Elofsson

  DOI：10.3390/biom11010055

  日期：——

  Pseudomonas aeruginosa is an opportunistic bacterial pathogen that employs its type III secretion system (T3SS) during the acute phase of infection to translocate cytotoxins into the host cell cytoplasm to evade the immune system. The PcrV protein is located at the tip of the T3SS, facilitates the integration of pore-forming proteins into the eukaryotic cell membrane, and is required for translocation of cytotoxins into the host cell. In this study, we used surface plasmon resonance screening to identify small molecule binders of PcrV. A follow-up structure-activity relationship analysis resulted in PcrV binders that protect macrophages in a P. aeruginosa cell-based infection assay. Treatment of P. aeruginosa infections is challenging due to acquired, intrinsic, and adaptive resistance in addition to a broad arsenal of virulence systems such as the T3SS. Virulence blocking molecules targeting PcrV constitute valuable starting points for development of next generation antibacterials to treat infections caused by P. aeruginosa.

  铜绿假单胞菌是一种机会性细菌病原体，它在感染的急性阶段利用其III型分泌系统（T3SS）将细胞毒素转运到宿主细胞胞质中，以逃避免疫系统。PcrV蛋白位于T3SS的顶端，促进孔形成蛋白与真核细胞膜的整合，并且需要将细胞毒素转运到宿主细胞中。在这项研究中，我们使用表面等离子共振筛选识别PcrV的小分子结合物。随后进行的结构-活性关系分析得出了能在基于P. aeruginosa细胞的感染实验中保护巨噬细胞的PcrV结合物。治疗P. aeruginosa感染具有挑战性，因为除了广泛的毒力系统（如T3SS）外，还存在获得性、固有性和适应性抗性。针对PcrV的毒力阻断分子为开发下一代抗菌剂治疗由铜绿假单胞菌引起的感染提供了宝贵的起点。
• Naked-Eye Bead Property Estimation Using a Red Safety-Catch Linker
  作者：Philipp Heidler、Andreas Link

  DOI：10.1071/ch04262

  日期：——

  The attachment of linker molecules to polymer beads used as insoluble supports for organic synthesis is a frequent requirement. Defined immobilization of these linker molecules before loading selected building blocks is crucial for subsequent transformations. Therefore, the control of the linker attachment is a central task. Because the molecular bodies of linkers are not incorporated in the final

  将接头分子连接到用作有机合成不溶性载体的聚合物珠粒上是一种常见的要求。在加载选定的构建块之前确定这些连接分子的固定对于后续转化至关重要。因此，链接器附件的控制是一项中心任务。由于连接体的分子体不掺入最终分子中，因此它们通常可以被替换或修饰，而不会影响最终释放的产物的结构。因此，寻找已建立的连接分子的有色替代物似乎很简单。通过使用彩色接头，可以对珠子进行目视检查，从而在连接后快速评估属性并监测合成过程中的损失。这个非常简单的估计没有经过验证的加载确定，但它是直接和非破坏性反应控制的有用元素，具有普遍适用性。在这里，我们提出了一种红色偶氮染料作为 Kenner 安全捕获接头的替代品。
• Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models
  作者：William Nguyen、Jonathan Jacobson、Kate E. Jarman、Helene Jousset Sabroux、Leigh Harty、James McMahon、Sharon R. Lewin、Damian F. Purcell、Brad E. Sleebs

  DOI：10.1021/acs.jmedchem.9b00462

  日期：2019.5.23

  The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.