(5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetic acid | 25055-51-0

• 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-acetic acid
• 英文别名: 2-(5-Bromo-1-methylindol-3-yl)-2-oxoacetic acid；2-(5-bromo-1-methylindol-3-yl)-2-oxoacetic acid
• CAS: 25055-51-0
• 化学式: C₁₁H₈BrNO₃
• 分子量: 282.093
• InChiKey: CYTDBQOCDBKESL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 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：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetic acid 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 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 0.5h， 生成 (5-bromo-1-methyl-1H-indol-3-yl)[3-(5-fluoro-1-methyl-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl]methanone
  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-1-甲基吲哚 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 16.0h， 生成 (5-bromo-1-methyl-1H-indol-3-yl)-oxo-acetic acid
  参考文献：
  名称：

  具有抗胰腺癌细胞增殖活性的 1,2,4-恶二唑 Topsentin 类似物，靶向 GSK3β 激酶

  摘要：

  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

  DOI：

  10.1002/cmdc.202000752

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
• 1,2,4-Oxadiazole topsentin analogs as staphylococcal biofilm inhibitors targeting the bacterial transpeptidase sortase A
  作者：Barbara Parrino、Daniela Carbone、Stella Cascioferro、Camilla Pecoraro、Elisa Giovannetti、Dongmei Deng、Veronica Di Sarno、Simona Musella、Giulia Auriemma、Maria Grazia Cusimano、Domenico Schillaci、Girolamo Cirrincione、Patrizia Diana

  DOI：10.1016/j.ejmech.2020.112892

  日期：2021.1

  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.