1-Bromo-2-[2-(2-fluoroethoxy)ethoxy]ethane | 1039399-97-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-Bromo-2-[2-(2-fluoroethoxy)ethoxy]ethane
• 英文别名: 1-(2-bromoethoxy)-2-(2-fluoroethoxy)ethane
• CAS: 1039399-97-7
• 化学式: C₆H₁₂BrFO₂
• 分子量: 215.062
• InChiKey: MWUYQSFLAKMUHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.38
• 重原子数：
  10.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-Bromo-2-[2-(2-fluoroethoxy)ethoxy]ethane 在 potassium carbonate 、 三氟乙酸 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

  摘要：

  小说sigma-2 配体1b在DU145细胞中诱导G1期细胞周期停滞并显示抗增殖活性。

  DOI：

  10.1039/c5md00079c

文献信息

• In Silico and In Vitro Study towards the Rational Design of 4,4′-Disarylbisthiazoles as a Selective α-Synucleinopathy Biomarker
  作者：Bright C. Uzuegbunam、Junhao Li、Wojciech Paslawski、Wolfgang Weber、Per Svenningsson、Hans Ågren、Behrooz Hooshyar Yousefi

  DOI：10.3390/ijms242216445

  日期：——

  The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4′-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies, a focused library of 23 halogen-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB and [3H]DCVJ. The DABTAs were obtained with an overall chemical yield of 15–71%, and showed a calculated lipophilicity of 2.5–5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1–4.9 nM and up to 20–3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo, and translational research and for further in vitro experiments on human-derived protein aggregates.

  α-突触核蛋白病是一组以α-突触核蛋白聚集体（α-syn）在大脑中沉积为特征的神经退行性疾病。目前，还没有合适的示踪剂能对这些疾病进行明确的早期诊断。我们报告了基于 4,4′-二芳基双噻唑（DABTA）支架的候选药物，它们对 α-syn 具有高亲和力，对 Aβ 和 tau 纤维具有出色的选择性。根据之前的硅学研究，我们制备了一个由 23 种含卤素和 O-甲基化的 DABTAs 组成的重点库。这些 DABTAs 是通过改进的两步 Hantzsch 噻唑合成法合成的，经过表征并用于与 [3H]PiB 和 [3H]DCVJ 的竞争性结合试验。DABTAs 的总化学收率为 15-71%，计算得出的亲油性为 2.5-5.7。这些配体与 [3H]PiB 和 [3H]DCVJ 对 α-syn 均表现出极佳的亲和力：Ki 0.1-4.9 nM，对 Aβ 和 tau 纤维的选择性高达 20-3900 倍。由此可以得出结论，硅学模拟有助于新一代 DABTAs 的合理设计。我们鼓励在下一步对这些线索进行进一步研究：用放射性同位素（如氟-18 或碳-11）对配体进行放射性标记，用于体内、体外和转化研究，以及对源自人类的蛋白质聚集体进行进一步的体外实验。