2-氨基-6-叔-丁氧基羰基氨基苯并噻唑 | 372096-66-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 2-氨基-6-叔-丁氧基羰基氨基苯并噻唑
• 英文名称: tert-butyl N-(2-amino-1,3-benzothiazol-6-yl)carbamate
• 英文别名: 2-amino-6-tert-butoxycarbonylaminobenzothiazole；Carbamic acid, (2-amino-6-benzothiazolyl)-, 1,1-dimethylethyl ester
• CAS: 372096-66-7
• 化学式: C₁₂H₁₅N₃O₂S
• 分子量: 265.336
• InChiKey: SUPUIAUSUYHJPS-UHFFFAOYSA-N

物化性质

• 密度：
  1.343±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氨基-6-叔-丁氧基羰基氨基苯并噻唑 、 2-氯-5-硝基苯甲酰氯 在 2,4-滴二甲胺盐 作用下， 以85%的产率得到N-[(6-tert-butoxycarbonylamino)benzothiazol-2-yl]-(2-chloro-5-nitrophenyl)carboxamide
  参考文献：
  名称：

  PPAR-gamma modulator

  摘要：

  以下化学式的化合物或其药理学上可接受的盐：其中A代表苯基或类似物，B代表芳基或类似物，X代表氧原子或类似物，n代表0或1。该化合物是一种PPAR &ggr; 调节剂，用于治疗逆行性骨质疏松症，通过抑制脂肪细胞的过度分化并促进干细胞向成骨细胞的形成和分化，以及用于糖尿病而不具有过度脂肪生成、肝功能障碍、血管紊乱、心脏疾病等特征。

  公开号：

  US20030134859A1

文献信息

• Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound
  作者：Tatiana A. Giovannucci、Florian A. Salomons、Martin Haraldsson、Lotta H. M. Elfman、Malin Wickström、Patrick Young、Thomas Lundbäck、Jürgen Eirich、Mikael Altun、Rozbeh Jafari、Anna-Lena Gustavsson、John Inge Johnsen、Nico P. Dantuma

  DOI：10.1038/s41419-021-04191-9

  日期：——

  Malignant cells display an increased sensitivity towards drugs that reduce the function of the ubiquitin-proteasome system (UPS), which is the primary proteolytic system for destruction of aberrant proteins. Here, we report on the discovery of the bioactivatable compound CBK77, which causes an irreversible collapse of the UPS, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death. CBK77 caused accumulation of ubiquitin-dependent, but not ubiquitin-independent, reporter substrates of the UPS, suggesting a selective effect on ubiquitin-dependent proteolysis. In a genome-wide CRISPR interference screen, we identified the redox enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) as a critical mediator of CBK77 activity, and further demonstrated its role as the compound bioactivator. Through affinity-based proteomics, we found that CBK77 covalently interacts with ubiquitin. In vitro experiments showed that CBK77-treated ubiquitin conjugates were less susceptible to disassembly by deubiquitylating enzymes. In vivo efficacy of CBK77 was validated by reduced growth of NQO1-proficient human adenocarcinoma cells in nude mice treated with CBK77. This first-in-class NQO1-activatable UPS inhibitor suggests that it may be possible to exploit the intracellular environment in malignant cells for leveraging the impact of compounds that impair the UPS.

  恶性细胞对降低泛素蛋白酶体系统（UPS）功能的药物表现出增加的敏感性，UPS是异常蛋白质降解的主要蛋白质系统。在这里，我们报告了生物活化化合物CBK77的发现，它导致UPS的不可逆性崩溃，伴随着泛素化蛋白的普遍积累和caspase依赖的细胞死亡。CBK77导致了依赖泛素而非独立于泛素的UPS报告底物的积累，表明对依赖泛素的蛋白质降解具有选择性影响。在全基因组CRISPR干扰筛选中，我们确定了氧化还原酶NAD(P)H：喹啉醌还原酶1（NQO1）作为CBK77活性的关键介导体，并进一步证明了其作为化合物生物活化剂的作用。通过亲和力基础蛋白质组学，我们发现CBK77与泛素发生共价作用。体外实验显示，CBK77处理后的泛素结合物对去泛素化酶的解聚作用较不敏感。在NQO1-proficient人类腺癌细胞中，用CBK77处理的裸鼠显示了CBK77的体内有效性。这种首创的NQO1活化的UPS抑制剂表明，可能可以利用恶性细胞内部环境来增强影响破坏UPS的化合物的作用。

• PPAR (GAMMA) MODULATORS
  申请人：Sankyo Company, Limited

  公开号：EP1277729A1

  公开（公告）日：2003-01-22

  [Subject] The present invention has a purpose for providing a PPAR γ modulator which can be a therapeutic agent for retrograde osteoporosis in which excessive differentiation of adipocytes was inhibited and formation and differentiation of osteoblasts from stem cells is facilitated or that for diabetes mellitus without characteristics such as excessive adipogenesis, liver dysfunction, vascular disorders, heart diseases and the like. [Solution] A compound of the following formula or a pharmacologically acceptable salt thereof: wherein A represents a phenyl group or the like, B represents an aryl group or the like, X represents an oxygen atom or the like, and n represents 0 or 1.

  主题 本发明的目的在于提供一种PPAR γ调节剂，该调节剂可作为逆行性骨质疏松症的治疗药物，在逆行性骨质疏松症中，脂肪细胞的过度分化受到抑制，而干细胞的成骨细胞的形成和分化得到促进，或者可作为无过度脂肪生成、肝功能障碍、血管紊乱、心脏病等特征的糖尿病的治疗药物。 [解决方案］ 下式化合物或其药理学上可接受的盐： 其中 A 代表苯基或类似物，B 代表芳基或类似物，X 代表氧原子或类似物，n 代表 0 或 1。
• PPAR-gamma modulator
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20030134859A1

  公开（公告）日：2003-07-17

  A compound of the following formula or a pharmacologically acceptable salt thereof: 1 wherein A represents a phenyl group or the like, B represents an aryl group or the like, X represents an oxygen atom or the like, and n represents 0 or 1. The compound is a PPAR &ggr; modulator which is a therapeutic agent for retrograde osteoporosis in which excessive differentiation of adipocytes is inhibited and formation and differentiation of osteoblasts from stem cells is facilitated, and for diabetes mellitus without characteristics such as excessive adipogenesis, liver dysfunction, vascular disorders, heart diseases and the like.

  以下化学式的化合物或其药理学上可接受的盐：其中A代表苯基或类似物，B代表芳基或类似物，X代表氧原子或类似物，n代表0或1。该化合物是一种PPAR &ggr; 调节剂，用于治疗逆行性骨质疏松症，通过抑制脂肪细胞的过度分化并促进干细胞向成骨细胞的形成和分化，以及用于糖尿病而不具有过度脂肪生成、肝功能障碍、血管紊乱、心脏疾病等特征。