4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzonitrile
• 英文别名: 4-(5,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)benzonitrile
• 化学式: C₁₆H₁₃N₃S
• 分子量: 279.365
• InChiKey: FMIBJWXCPRCCDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzonitrile 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以90%的产率得到4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzylamine
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors

  摘要：

  Since activation of p53 in response to cytotoxic stress may have proapoptotic or protective effects depending on the nature of the injury, inhibitors of p53 may have therapeutic interest as modulators of chemotherapy toxicity or efficacy. In an attempt to identify novel p53 inhibitors, a quality collection of compounds structurally related to pifithrin-beta were designed and synthesized as potential inhibitors of p53. The biochemical and biological evaluations supported that compounds of the tetrahydrobenzothiazole series were inhibitors of the p53 transcriptional activity and were effective in enhancing paclitaxel-induced apoptosis. In contrast, in spite of the increased cytotoxic potency, selected compounds of the benzothiazole series were not able to modulate the transcriptional activity of p53, as indicated by lack of change of p21 expression. The therapeutic interest of the compounds of the former series in combination with taxanes was confirmed in a human tumor xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.039
• 作为产物：
  描述：

  环己酮 在 碘 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors

  摘要：

  Since activation of p53 in response to cytotoxic stress may have proapoptotic or protective effects depending on the nature of the injury, inhibitors of p53 may have therapeutic interest as modulators of chemotherapy toxicity or efficacy. In an attempt to identify novel p53 inhibitors, a quality collection of compounds structurally related to pifithrin-beta were designed and synthesized as potential inhibitors of p53. The biochemical and biological evaluations supported that compounds of the tetrahydrobenzothiazole series were inhibitors of the p53 transcriptional activity and were effective in enhancing paclitaxel-induced apoptosis. In contrast, in spite of the increased cytotoxic potency, selected compounds of the benzothiazole series were not able to modulate the transcriptional activity of p53, as indicated by lack of change of p21 expression. The therapeutic interest of the compounds of the former series in combination with taxanes was confirmed in a human tumor xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.039

文献信息

• Imidazo[2,1-<i>b</i>]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor
  作者：Michael S. Christodoulou、Federico Dapiaggi、Francesca Ghiringhelli、Stefano Pieraccini、Maurizio Sironi、Marianna Lucafò、Debora Curci、Giuliana Decorti、Gabriele Stocco、Chandra Sekhar Chirumamilla、Wim Vanden Berghe、Patrick Balaguer、Benoît Y. Michel、Alain Burger、Egle M. Beccalli、Daniele Passarella、Nadine Martinet

  DOI：10.1021/acsmedchemlett.7b00527

  日期：2018.4.12

  of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]benzoimidazole derivatives were identified for their ability to modulate GCR transactivation and anti-inflammatory transrepression effects utilizing GCR and NF-κB specific reporter gene assays. Modeling studies on the crystallographic structure of the GCR ligand binding domain provided three new analogues bearing the tetrahydroimidazo[2,1-b]benzothiazole

  糖皮质激素受体（GCR）反式激活报告基因试验被用作对1200种化合物的多元化文库的初步高通量筛选，以评估其作为GCR拮抗剂的作用。一类咪唑并[2,1- b ]苯并噻唑和咪唑并[2,1- b ]苯并咪唑衍生物利用GCR和NF-κB特异的报告基因检测方法，具有调节GCR反式激活和抗炎性抑制作用的能力。GCR配体结合域的晶体结构的模型研究提供了三个带有四氢咪唑[2,1- b]的新类似物能够在地塞米松（DEX）存在下拮抗GCR的]苯并噻唑支架，并且还定义了它们在GCR结构中的假定结合。在用新类似物处理的细胞上，GCR本身及其靶基因GILZ的mRNA水平测量均显示出GCR反式激活抑制作用，因此暗示了GCR的潜在变构抑制作用。
• Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors
  作者：Michael S. Christodoulou、Francesco Colombo、Daniele Passarella、Gabriella Ieronimo、Valentina Zuco、Michelandrea De Cesare、Franco Zunino

  DOI：10.1016/j.bmc.2011.01.039

  日期：2011.3

  Since activation of p53 in response to cytotoxic stress may have proapoptotic or protective effects depending on the nature of the injury, inhibitors of p53 may have therapeutic interest as modulators of chemotherapy toxicity or efficacy. In an attempt to identify novel p53 inhibitors, a quality collection of compounds structurally related to pifithrin-beta were designed and synthesized as potential inhibitors of p53. The biochemical and biological evaluations supported that compounds of the tetrahydrobenzothiazole series were inhibitors of the p53 transcriptional activity and were effective in enhancing paclitaxel-induced apoptosis. In contrast, in spite of the increased cytotoxic potency, selected compounds of the benzothiazole series were not able to modulate the transcriptional activity of p53, as indicated by lack of change of p21 expression. The therapeutic interest of the compounds of the former series in combination with taxanes was confirmed in a human tumor xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.