(4-溴苯氧基)乙酰氯 | 16738-06-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: (4-溴苯氧基)乙酰氯
• 中文别名: 乙酰氯,(4-溴苯氧基)-
• 英文名称: 4-bromophenoxyacetyl chloride
• 英文别名: (4-bromo-phenoxy)-acetyl chloride；(4-Brom-phenoxy)-acetylchlorid；4-Brom-phenoxyessigsaeure-chlorid；<4-Brom-phenoxy>-acetylchlorid；(4-Bromophenoxy)acetyl chloride；2-(4-bromophenoxy)acetyl chloride
• CAS: 16738-06-0
• 化学式: C₈H₆BrClO₂
• mdl: MFCD02295745
• 分子量: 249.491
• InChiKey: WGNGWDLGDORSKX-UHFFFAOYSA-N

物化性质

• 沸点：
  154 °C(Press: 12 Torr)
• 密度：
  1.613±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  (4-溴苯氧基)乙酰氯 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.75h， 生成 N-(2-(1-acetyl-1H-benzo[d]imidazol-2-yl)ethyl)-2-(4-bromophenoxy)acetamide
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure–Activity Relationships of Potent Noncovalent and Nonpeptidic Cruzain Inhibitors as Anti-Trypanosoma cruzi Agents

  摘要：

  The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for the treatment of Chagas' disease. Herein, we report the lead optimization of a class of noncovalent cruzain inhibitors, starting from an inhibitor previously cocrystallized with the enzyme (K(i) = 0.8 μM). With the goal of achieving a better understanding of the structure-activity relationships, we have synthesized and evaluated a series of over 40 analogues, leading to the development of a very promising competitive inhibitor (8r, IC50 = 200 nM, K(i) = 82 nM). Investigation of the in vitro trypanocidal activity and preliminary cytotoxicity revealed the potential of the most potent cruzain inhibitors in guiding further medicinal chemistry efforts to develop drug candidates for Chagas' disease.

  DOI：

  10.1021/jm401709b
• 作为产物：
  描述：

  对溴苯氧乙酸 在 氯化亚砜 作用下， 生成 (4-溴苯氧基)乙酰氯
  参考文献：
  名称：

  Synthesis, Structure and Biological Activities of Novel Triazole Compounds Containing Ester Group

  摘要：

  合成了含有酯基的新型三唑化合物。通过红外光谱、1H NMR 和元素分析确认了这些化合物的结构。通过 X 射线衍射，确定了化合物 (1H-1,2,4- triazol-1-yl)methyl 3-(2,4-dichlorophenyl)propanoate（化合物 3c）的单晶结构。它呈单斜晶系结晶，空间群为 P2(1)/c，a = 1.0814(2) nm，b = 0.64514(13) nm，c = 1.8698(4) nm，b = 101.05(3)° ，Z = 4，V = 1.2802(5) nm3，Dc = 1.557 Mg/m3，μ = 0.508 mm-1，F(000) = 616，最终 R1 = 0.0700。分子间氢键和 p-p 堆叠相互作用在晶格中退出，促进了晶体结构的稳定。生物测试结果表明，这些化合物具有一定的杀菌活性。

  DOI：

  10.14233/ajchem.2014.16088

文献信息

• Identification of Anthranilic Acid Derivatives as a Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase
  作者：Thomas Nittoli、Kevin Curran、Shabana Insaf、Martin DiGrandi、Mark Orlowski、Rajiv Chopra、Atul Agarwal、Anita Y. M. Howe、Amar Prashad、M. Brawner Floyd、Bernard Johnson、Alan Sutherland、Karen Wheless、Boris Feld、John O'Connell、Tarek S. Mansour、Jonathan Bloom

  DOI：10.1021/jm061428x

  日期：2007.5.1

  A series of potent anthranilic acid-based inhibitors of the hepatitis C NS5B polymerase has been identified. The inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site as determined by X-ray crystallography of the enzyme-inhibitor complex. Guided by both molecular modeling and traditional SAR, the enzyme activity of the initial hit was improved by approximately

  已鉴定出一系列强效邻氨基苯甲酸丙型肝炎 NS5B 聚合酶抑制剂。通过酶抑制剂复合物的 X 射线晶体学测定，抑制剂与 NS5B 上拇指和手掌区域之间与活性位点相邻的位点结合。在分子建模和传统 SAR 的指导下，初始命中的酶活性提高了约 100 倍，产生了一系列有效且选择性的 NS5B 抑制剂，IC50 值低至 10 nM。这些化合物也是培养的 HUH7 细胞中 HCV 复制子的抑制剂。
• Synthesis and biological evaluation of aryloxyacetamide derivatives as neuroprotective agents
  作者：Yan Zhong、Yi Xu、Ai-Xia Zhang、Xiao-Feng Li、Zhao-Ying Xu、Ping Li、Bin Wu

  DOI：10.1016/j.bmcl.2016.03.094

  日期：2016.5

  series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and synthesized. Their protective activities against the glutamate-induced cell death were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and 14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0, 10muM)

  设计并合成了一系列新的芳氧基乙酰胺衍生物10a-s和14a-m。在分化的大鼠嗜铬细胞瘤细胞（PC12细胞）中研究了它们对谷氨酸诱导的细胞死亡的保护活性。大多数化合物表现出神经保护作用，尤其是对10m，10r，14b和14c表现出神经保护作用，在三种剂量（0.1、1.0、10μM）下，PC12细胞都有潜在的保护作用。MTT分析，Hoechst 33342 / PI双重染色和高含量筛选（HCS）显示，用10m，10r，14b和14c预处理细胞以剂量依赖的方式显着降低了细胞凋亡的程度。蛋白质印迹分析的结果表明，这些化合物通过caspase-3途径抑制了谷氨酸诱导的PC12细胞凋亡。这些化合物可以是用于进一步发现用于治疗脑缺血性中风的神经保护剂的先导化合物。还介绍了基本的结构-活性关系。
• Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors
  作者：Fenglong Zhang、Jin Du、Qing Wang、Qinghua Hu、Jiong Zhang、Dazhong Ding、Yaxue Zhao、Fei Yang、Enduo Wang、Huchen Zhou

  DOI：10.1039/c3ob40236c

  日期：——

  Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC50 = 13.7 μM). Aided by ligand–protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.

  非洲锥虫病(Human African trypanosomiasis, HAT)是热带地区最为忽视的致死性疾病之一,若不及时治疗,将会有致命风险。迫切需要新的治疗药物,特别是新的化学类别中的药物。白氨酰-tRNA合成酶(Leucyl-tRNA synthetase, LeuRS)作为一个最近的临床验证的抗菌靶点,受到了广泛关注。我们的研究团队前期报道了针对编辑位点的苯并氧杂硼啶类和针对合成位点的吡咯烷酮类刚果锥虫LeuRS(TbLeuRS)抑制剂。在此,我们报道了N-(4-磺酰胺基苯基)硫脲作为新型TbLeuRS抑制剂的发现。借鉴于aa-AMP和aa-AMS中的氨酰基和腺苷基结构的R1和R2基团,经过优化设计,显著提高了13倍的抑制活性(化合物19, IC50 = 13.7 μM)。通过配体-蛋白对接辅助,预测并验证了在苯环上的1,3-取代,能显著提高活性(化合物59, IC50 = 1.1 μM)。这项工作为探索新型TbLeuRS抑制剂提供了一个新的骨架,这些抑制剂可能成为治疗HAT的潜在药物。
• ROLES OF MODULATORS OF INTERSECTIN-CDC42 SIGNALING IN ALZHEIMER'S DISEASE
  申请人：East Carolina University

  公开号：US20190091184A1

  公开（公告）日：2019-03-28

  Methods of treating Alzheimer's disease and other neurodegenerative and/or neurocognitive and/or neurodevelopmental diseases are described. The methods comprise the administration of compounds that modulate an activity of cell division control protein 42 (Cdc42), such as the interaction between Cdc42 and intersectin (ITSN). Exemplary modulator compounds include thioureas, disulfonamides of fused aromatic systems (e.g., benzofuran), and acyl hydrazones, among others. Some of the modulator compounds act as activators of Cdc42, while others act as inhibitors. In some cases, the modulator compound has dual functionality and the ability of the modulator compound to act as an inhibitor or activator depends on whether or not Cdc42 is already activated in a particular disease stage or biological environment by an upstream activating signal of Cdc42.

  描述了治疗阿尔茨海默病和其他神经退行性和/或神经认知和/或神经发育疾病的方法。这些方法包括给予调节细胞分裂控制蛋白42（Cdc42）活性的化合物，例如Cdc42与交叉素（ITSN）之间的相互作用。示例调节剂化合物包括硫脲、融合芳香系统的二磺酰胺（例如苯并呋喃）和酰基肼等。其中一些调节剂化合物作为Cdc42的激活剂，而另一些作为抑制剂。在某些情况下，调节剂化合物具有双重功能，调节剂化合物作为抑制剂或激活剂的能力取决于Cdc42是否已经通过Cdc42的上游激活信号在特定疾病阶段或生物环境中被激活。
• Structure-based design, synthesis and evaluation of 2,4-diaminopyrimidine derivatives as novel caspase-1 inhibitors
  作者：Shivani Patel、Palmi Modi、Vishal Ranjan、Mahesh Chhabria

  DOI：10.1016/j.bioorg.2018.03.019

  日期：2018.8

  caspase-1 may provide a potential therapeutic strategy for the treatment of chronic inflammatory diseases. Here we have reported structure-based design, synthesis and biological evaluation of 2,4-diaminopyrimidine derivatives (6a-6w) as potential caspase-1 inhibitors. Six compounds 6m, 6n, 6o, 6p, 6q and 6r showed significant enzymatic inhibition with IC50 ranging from 0.022 to 0.078 µM. These compounds

  白介素-1β转化酶通过使促炎性细胞因子IL-1β，IL-18和IL-33成熟，从而导致多种炎症和自身免疫性疾病。因此，抑制caspase-1可能为慢性炎性疾病的治疗提供潜在的治疗策略。在这里，我们已经报告了作为潜在caspase-1抑制剂的2,4-二氨基嘧啶衍生物（6a-6w）的基于结构的设计，合成和生物学评估。六种化合物6m，6n，6o，6p，6q和6r对IC 5 0表现出明显的酶抑制作用范围为0.022至0.078 µM。这些化合物在亚微摩尔浓度下也显示出优异的细胞效价。此外，分子对接研究提供了对caspase-1抑制特异的有用的结合见解。所有这些结果表明，化合物6m，6n和6o可能是开发新型caspase-1抑制剂作为抗炎药的潜在原因。