5-(1-methyl-1H-indol-3-yl)-1,3,4-thiadiazol-2-amine | 885521-91-5

• 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-(1-methyl-1H-indol-3-yl)-1,3,4-thiadiazol-2-amine
• 英文别名: 2-Amino-5-(1-methyl-3-indolyl)-1,3,4-thiadiazole；5-(1-methylindol-3-yl)-1,3,4-thiadiazol-2-amine
• CAS: 885521-91-5
• 化学式: C₁₁H₁₀N₄S
• 分子量: 230.293
• InChiKey: NIXXMFLOHPCPTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  56.73
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-(1-methyl-1H-indol-3-yl)-1,3,4-thiadiazol-2-amine 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 29.0h， 生成 6-(2,5-dimethoxyphenyl)-2-(1-methyl-1H-indol-3-yl)imidazo[2,1-b] [1,3,4]thiadiazole-5-carbaldehyde
  参考文献：
  名称：

  Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells

  摘要：

  A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 mu M, and 0.29-12.2 mu M, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112088
• 作为产物：
  描述：

  3-氰基吲哚 在 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 5-(1-methyl-1H-indol-3-yl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  2,6-二取代的咪唑并[2,1- b ] [1,3,4]噻二唑衍生物作为有效的葡萄球菌生物膜抑制剂

  摘要：

  高效合成了36种新型的2-（6-苯基咪唑并[2，-1- b ] [1,3,4]噻二唑-2-基）-1 H-吲哚并评估了它们的抗生物膜特性。革兰氏阳性细菌参考菌株金黄色葡萄球菌ATCC 25923，金黄色葡萄球菌ATCC 6538和表皮葡萄球菌ATCC 12228，以及革兰氏阴性铜绿假单胞菌ATCC 15442和大肠杆菌ATCC25922。这些新化合物中的许多能够抑制生物膜的形成。的测试葡萄球菌菌株显示BIC 50低于10μg/ ml。尤其是导数9c和9h分别显示出对金黄色葡萄球菌ATCC 25923的显着抗生物膜活性，BIC 50值分别为0.5和0.8μg / ml，而化合物9aa对金黄色葡萄球菌ATCC 6538最有效，BIC 50为0.3μg/ ml。值得注意的是，这些化合物在生物膜形成的早期阶段显示出作用，而不会影响相同菌株的成熟生物膜和浮游生物的生存能力。它们在不干扰细菌以自由生命形

  DOI：

  10.1016/j.ejmech.2019.02.007

文献信息

• 2,6-Disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent staphylococcal biofilm inhibitors
  作者：Stella Cascioferro、Barbara Parrino、Giovanna Li Petri、Maria Grazia Cusimano、Domenico Schillaci、Veronica Di Sarno、Simona Musella、Elisa Giovannetti、Girolamo Cirrincione、Patrizia Diana

  DOI：10.1016/j.ejmech.2019.02.007

  日期：2019.4

  25922. Many of these new compounds, were able to inhibit biofilm formation of the tested staphylococcal strains showing BIC50 lower than 10 μg/ml. In particular, derivatives 9c and 9h showed remarkable anti-biofilm activity against S. aureus ATCC 25923 with BIC50 values of 0.5 and 0.8 μg/ml, respectively, whereas compound 9aa was the most potent against S. aureus ATCC 6538, with a BIC50 of 0.3 μg/ml. Remarkably

  高效合成了36种新型的2-（6-苯基咪唑并[2，-1- b ] [1,3,4]噻二唑-2-基）-1 H-吲哚并评估了它们的抗生物膜特性。革兰氏阳性细菌参考菌株金黄色葡萄球菌ATCC 25923，金黄色葡萄球菌ATCC 6538和表皮葡萄球菌ATCC 12228，以及革兰氏阴性铜绿假单胞菌ATCC 15442和大肠杆菌ATCC25922。这些新化合物中的许多能够抑制生物膜的形成。的测试葡萄球菌菌株显示BIC 50低于10μg/ ml。尤其是导数9c和9h分别显示出对金黄色葡萄球菌ATCC 25923的显着抗生物膜活性，BIC 50值分别为0.5和0.8μg / ml，而化合物9aa对金黄色葡萄球菌ATCC 6538最有效，BIC 50为0.3μg/ ml。值得注意的是，这些化合物在生物膜形成的早期阶段显示出作用，而不会影响相同菌株的成熟生物膜和浮游生物的生存能力。它们在不干扰细菌以自由生命形
• 10.1080/1061186x.2024.2385557
  作者：Pecoraro, Camilla、Carbone, Daniela、Scianò, Fabio、Terrana, Francesca、Xu, Geng、Bergonzini, Cecilia、Roeten, Margot S. F.、Cascioferro, Stella、Cirrincione, Girolamo、Diana, Patrizia、Giovannetti, Elisa、Parrino, Barbara

  DOI：10.1080/1061186x.2024.2385557

  日期：——
• Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells
  作者：Stella Cascioferro、Giovanna Li Petri、Barbara Parrino、Daniela Carbone、Niccola Funel、Cecilia Bergonzini、Giulia Mantini、Henk Dekker、Daan Geerke、Godefridus J. Peters、Girolamo Cirrincione、Elisa Giovannetti、Patrizia Diana

  DOI：10.1016/j.ejmech.2020.112088

  日期：2020.3

  A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 mu M, and 0.29-12.2 mu M, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Novel [1,3,4]Thiadiazole[3,2-a]pyrimidin-5-ones as Promising Biofilm Dispersal Agents against Relevant Gram-Positive and Gram-Negative Pathogens
  作者：Daniela Carbone、Camilla Pecoraro、Fabio Scianò、Valentina Catania、Domenico Schillaci、Barbara Manachini、Stella Cascioferro、Patrizia Diana、Barbara Parrino

  DOI：10.3390/md22030133

  日期：——

  bioactive molecules, including numerous derivatives with antibiofilm activity. In this study, we reported the synthesis and the biological evaluation of a new series of twenty-two thiadiazopyrimidinone derivatives obtained by using a hybridization approach combining relevant chemical features of two important classes of marine compounds: nortopsentin analogues and Essramycin derivatives. The synthesized

  由于生物膜相关感染对传统抗菌疗法具有耐药性，因此在医疗保健环境中构成了重大挑战。在过去的十年中，海洋环境一直是生物活性分子的宝贵来源，其中包括许多具有抗生物膜活性的衍生物。在这项研究中，我们报道了一系列新的二十二种噻二唑嘧啶酮衍生物的合成和生物学评价，这些衍生物是通过结合两类重要海洋化合物的相关化学特征的杂交方法获得的：诺托普森汀类似物和艾斯拉霉素衍生物。体外测试了合成的化合物抑制生物膜形成和破坏各种细菌菌株成熟生物膜的能力。在测试的化合物中，衍生物8j对相关革兰氏阳性和革兰氏阴性病原体的预先形成的生物膜以及真菌白色念珠菌表现出显着的分散活性，显示BIC50值范围为17至40μg/mL。此外，在大蜡螟模型中体内测定了化合物8j的毒性和抗感染作用。结果揭示了抗感染特性和有利的毒性特征的良好组合，可用于治疗严重的慢性生物膜介导的感染。