(5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride | 143137-54-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride
• 英文别名: 2-(5-Bromo-1-methylindol-3-yl)-2-oxoacetyl chloride
• CAS: 143137-54-6
• 化学式: C₁₁H₇BrClNO₂
• 分子量: 300.539
• InChiKey: XNOQAIXWXINBTD-UHFFFAOYSA-N

物化性质

• 沸点：
  444.2±48.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  39.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N’-{[(5-bromo-1-methyl-1H-indol-3-yl)(oxo)acetyl]oxy}-1-methyl-1H-indole-3-carboximidamide
  参考文献：
  名称：

  1,2,4-Oxadiazole topsentin analogs as staphylococcal biofilm inhibitors targeting the bacterial transpeptidase sortase A

  摘要：

  The inhibition or prevention of biofilm formation represents an emerging strategy in the war against antibiotic resistance, interfering with key players in bacterial virulence. This approach includes the inhibition of the catalytic activity of transpeptidase sortase A (Srt A), a membrane enzyme responsible for covalently attaching a wide variety of adhesive matrix molecules to the peptidoglycan cell wall in Gram-positive strains. A new series of seventeen 1,2,4-oxadiazole derivatives was efficiently synthesized and screened as potential new anti-virulence agents. The ability of inhibiting biofilm formation was evaluated against both Gram-positive and Gram-negative pathogens. Remarkably, all these compounds inhibited S. aureus and/or P. aeruginosa biofilm formation in a dose dependent manner, with 50% biofilm inhibitory concentrations (BIC_50s) below 10 μM for the most active compounds. Inhibition of SrtA was validated as one of the possible mechanisms of action of these new 1,2,4-oxadiazole derivatives, in the tested Gram-positive pathogen, using a specific enzymatic assay for a recombinant S. aureus SrtA. The three most active compounds, eliciting BIC₅₀ values for S. aureus ATCC 25923 between 0.7 and 9.7 μM, showed a good activity toward the enzyme eliciting IC₅₀ values ranging from 2.2 to 10.4 μM.

  DOI：

  10.1016/j.ejmech.2020.112892
• 作为产物：
  描述：

  5-溴吲哚 在 potassium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetyl chloride
  参考文献：
  名称：

  双（吲哚基）三嗪酮，诺托普汀类似物的合成，抗癌评估和分子对接研究

  摘要：

  摘要设计并合成了一系列新的双吲哚基三酮重氮化合物和3,5-双（3'-吲哚基）三嗪酮作为抗癌剂。在体外针对四种不同的人类癌细胞系（如HeLa，MCF-7，MDA-MB-231和A549细胞系）筛选了它们的抗癌活性。其中，化合物17a和17b对人宫颈癌细胞系显示有效的细胞毒性，抑制（IC 50）值分别为4.6和1.3 µM。使用ADT 1.5.6工具进行的计算机模拟研究表明，与其余化合物相比，化合物17b的吲哚环与秋水仙碱活性位点残基Tyr312的独特π-π相互作用可能是其最大效价落后的有效原因，因为其余化合物均具有较高的活性。 图形概要

  DOI：

  10.1007/s11696-017-0372-8

文献信息

• 1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase
  作者：Daniela Carbone、Barbara Parrino、Stella Cascioferro、Camilla Pecoraro、Elisa Giovannetti、Veronica Di Sarno、Simona Musella、Giulia Auriemma、Girolamo Cirrincione、Patrizia Diana

  DOI：10.1002/cmdc.202000752

  日期：2021.2.4

  series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4‐oxadiazole moiety, was efficiently synthesized. All derivatives were pre‐screened for antiproliferative activity against the National Cancer Institute (NCI‐60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines

  高效合成了一系列新的topsentin类似物，其中天然铅的中心咪唑环被1,2,4-恶二唑部分取代。所有衍生物均针对美国国家癌症研究所 (NCI-60) 细胞系面板的抗增殖活性进行了预筛选。在各种胰腺导管腺癌 (PDAC) 细胞系中进一步研究了五种最有效的化合物，包括 SUIT-2、Capan-1 和 Panc-1 细胞，引发 EC 50微摩尔和亚微摩尔范围内的值，与细胞迁移的显着减少有关。这些显着的结果可能是由于这些新的 topsentin 类似物对上皮-间质转化标志物的影响，包括 SNAIL-1/2 和金属蛋白酶-9。此外，Annexin V-FITC 和碘化丙啶染色后的流式细胞术分析表明，这些衍生物增强了 PDAC 细胞的凋亡。与这些数据保持一致，PathScan 细胞内信号传导和 ELISA 阵列显示 caspase-3 和 PARP 的裂解以及 GSK3β 磷酸化的显着抑制，表明该
• Structural Simplification of Marine Natural Products: Discovery of Hamacanthin Derivatives Containing Indole and Piperazinone as Novel Antiviral and Anti-phytopathogenic-fungus Agents
  作者：Tienan Wang、Lin Li、Yanan Zhou、Aidang Lu、Hongyan Li、Jianxin Chen、Zhongyu Duan、Qingmin Wang

  DOI：10.1021/acs.jafc.1c04098

  日期：2021.9.8

  designed, synthesized, and studied on the antiviral and antifungal activities. Most of these compounds displayed higher antiviral activities than ribavirin. The antiviral activities of compounds 1a and 13e–13h are similar to or higher than that of ningnanmycin (perhaps the most efficient anti-plant-virus agent). Compound 13h was selected for further antiviral mechanism research via transmission electron

  随着植物病害的日益严重和病原体抗性的出现，迫切需要开发新型高效、环保的农药。海洋天然产物（MNP）资源丰富多样。基于 MNP 的结构简化是寻找新型农药候选物的重要策略。在这项工作中，海洋天然产物 6"-debromohamacanthin A ( 1a ) 被有效地制备并选择为母体结构。设计、合成了一系列金黄素衍生物，并研究了其抗病毒和抗真菌活性。大多数这些化合物显示出比利巴韦林更高的抗病毒活性。化合物1a和13e – 13h的抗病毒活性与宁南霉素（可能是最有效的抗植物病毒剂）相似或更高。通过透射电子显微镜、分子对接和荧光滴定，选择化合物13h进行进一步的抗病毒机制研究。结果表明，化合物13h可与TMV CP结合，干扰TMV CP与RNA的组装过程。此外，这些金黄素衍生物还对八种常见的农业病原体表现出广谱抑制作用。化合物1a、12b和12f具有优异的杀菌活性，可作为新的杀菌候选物进行进一步
• Synthesis and Antitumor Evaluation of Novel 5-Bromo Indole-Aryl Keto Hydrazide-Hydrazone Analogues
  作者：Durgesh Rudavath、Reddymasu Sreenivasulu、Srinivasa Rao Pinapati、Rudraraju Ramesh Raju

  DOI：10.14233/ajchem.2018.21114

  日期：——

  A wide variety of indole, substituted benzaldehyde linked keto hydrazide-hydrazone analogues were designed, synthesized and evaluated for their cytotoxicity against eight human cancer cell lines HeLa, A549, MCF-7, K562, HEK293, HT29, SF295 and HL60. All these synthesized compounds showed potent antitumor activities on the above eight human cancer cell lines. Among them, 6a and 6h compounds exhibited potent antitumor activity on HL 60 and A549 cancer cell lines with IC50 value of 3.913 and 4.838 μM than the standard drug cisplatin with IC50 values of 27 and 36 μM, respectively.

  本研究设计、合成了多种吲哚、取代苯甲醛连接的酮酰肼-腙类似物，并评估了它们对 HeLa、A549、MCF-7、K562、HEK293、HT29、SF295 和 HL60 八种人类癌细胞系的细胞毒性。所有这些合成化合物都对上述八种人癌细胞株显示出了强大的抗肿瘤活性。其中，6a 和 6h 化合物对 HL 60 和 A549 癌细胞株具有很强的抗肿瘤活性，其 IC50 值分别为 3.913 和 4.838 μM，高于标准药物顺铂的 IC50 值 27 和 36 μM。
• Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in Pancreatic Ductal Adenocarcinoma
  作者：Daniela Carbone、Michele De Franco、Camilla Pecoraro、Davide Bassani、Matteo Pavan、Stella Cascioferro、Barbara Parrino、Girolamo Cirrincione、Stefano Dall’Acqua、Stefania Sut、Stefano Moro、Valentina Gandin、Patrizia Diana

  DOI：10.3390/md21050288

  日期：——

  Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs). The results showed that most of derivatives totally inhibit PDK1 and PDK4. Molecular docking analysis was executed to predict the possible binding mode of these derivatives using ligand-based homology modeling technique. Evaluation of the capability of new triazines to inhibit the cell growth in 2D and 3D KRAS-wild-type (BxPC-3) and KRAS-mutant (PSN-1) PDAC cell line, was carried out. The results showed the capacity of the new derivatives to reduce cell growth with a major selectivity against KRAS-mutant PDAC PSN-1 on both cell models. These data demonstrated that the new triazine derivatives target PDK1 enzymatic activity and exhibit cytotoxic effects on 2D and 3D PDAC cell models, thus encouraging further structure manipulation for analogs development against PDAC.

  胰腺导管腺癌（PDAC）是主要的侵袭性癌症类型之一，具有预后晚和耐药性强的特点。在维持 PDAC 进展的主要因素中，细胞新陈代谢的改变已成为 PDAC 细胞增殖、侵袭和对标准化疗药物产生耐药性的关键因素。考虑到所有这些因素以及评估治疗 PDAC 的新方案的紧迫性，我们在本研究中报告了受海洋双吲哚生物碱启发合成的一系列新的吲哚基-7-氮杂吲哚基三嗪化合物。我们首先评估了新三嗪化合物抑制丙酮酸脱氢酶激酶（PDKs）酶活性的能力。结果表明，大多数衍生物能完全抑制 PDK1 和 PDK4。利用基于配体的同源建模技术进行了分子对接分析，以预测这些衍生物可能的结合模式。研究还评估了新型三嗪类化合物在二维和三维 KRAS 野生型（BxPC-3）和 KRAS 突变型（PSN-1）PDAC 细胞系中抑制细胞生长的能力。结果表明，新衍生物能够降低两种细胞模型中 KRAS 突变型 PDAC PSN-1 的细胞生长，并对其具有较大的选择性。这些数据表明，新的三嗪衍生物以 PDK1 酶活性为靶点，在二维和三维 PDAC 细胞模型上表现出细胞毒性作用，从而鼓励了针对 PDAC 类似物开发的进一步结构操作。
• Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma
  作者：Daniela Carbone、Michele De Franco、Camilla Pecoraro、Davide Bassani、Matteo Pavan、Stella Cascioferro、Barbara Parrino、Girolamo Cirrincione、Stefano Dall’Acqua、Stefano Moro、Valentina Gandin、Patrizia Diana

  DOI：10.3390/ijms24043679

  日期：——

  aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed,

  丙酮酸脱氢酶激酶 (PDK) 是丝氨酸/苏氨酸激酶，直接参与改变癌细胞代谢，导致癌症侵袭性和耐药性。二氯乙酸（DCA）是第一个进入II期临床的PDK抑制剂；然而，抗癌活性弱和药物剂量过高（100 mg/kg）相关的一些副作用导致其在临床应用中受到限制。基于分子杂交方法，设计、合成了一个小型 3-氨基-1,2,4-三嗪衍生物文库，并使用计算机、体外和体内测定对其 PDK 抑制活性进行了表征。生化筛选表明所有合成的化合物都是PDK的有效亚型选择性抑制剂。因此，分子模型研究表明，许多配体可以正确放置在 PDK1 的 ATP 结合位点内。有趣的是，2D 和 3D 细胞研究揭示了它们在低微摩尔剂量下诱导癌细胞死亡的能力，对人类胰腺 KRAS 突变癌细胞极其有效。细胞机制研究证实它们能够阻碍 PDK/PDH 轴，从而导致代谢/氧化还原细胞损伤，并最终引发癌细胞凋亡。值得注意的是，在高度侵袭性和转移性 KRAs