tert-butyl 4-(6-bromobenzothiazol-2-yl)piperazine-1-carboxylate | 1346626-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(6-bromobenzothiazol-2-yl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-(6-bromobenzo[d]thiazol-2-yl)piperazine-1-carboxylate；tert-butyl 4-(6-bromo-1,3-benzothiazol-2-yl)piperazine-1-carboxylate
• CAS: 1346626-81-0
• 化学式: C₁₆H₂₀BrN₃O₂S
• 分子量: 398.324
• InChiKey: DSXLOTFHQGIOMD-UHFFFAOYSA-N

物化性质

• 沸点：
  488.6±55.0 °C(Predicted)
• 密度：
  1.459±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(6-bromobenzothiazol-2-yl)piperazine-1-carboxylate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-phenyl-2-(piperazin-1-yl)benzothiazole
  参考文献：
  名称：

  Small molecules enhance functional O-mannosylation of Alpha-dystroglycan

  摘要：

  Alpha-dystroglycan (alpha-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of alpha-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of alpha-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of alpha-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of alpha-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of alpha-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of alpha-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.011
• 作为产物：
  描述：

  2-氯-6-溴苯并噻唑 、 N-Boc-哌嗪 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 4-(6-bromobenzothiazol-2-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Small molecules enhance functional O-mannosylation of Alpha-dystroglycan

  摘要：

  Alpha-dystroglycan (alpha-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of alpha-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of alpha-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of alpha-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of alpha-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of alpha-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of alpha-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.011

文献信息

• [EN] BICYCLIC HETEROARYL COMPOUNDS AS GPR119 MODULATORS<br/>[FR] COMPOSÉS HÉTÉROARYLES BICYCLIQUES EN TANT QUE MODULATEURS DE GPR119
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011140160A1

  公开（公告）日：2011-11-10

  Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, R2 and R4 are defined herein, are provided which are GPR119 G protein- coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  结构式I的新化合物：或其对映体、二对映体、互变异构体、前药或盐，其中A、D、Di、E、J、L、n、Q、R2和R4在此处被定义，提供了这些化合物是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病的进展方面是有用的。因此，本公开还涉及包含这些新化合物的组合物和使用任何这些新化合物或包含任何这些新化合物的组合物治疗与GPR119 G蛋白偶联受体活性相关的疾病或症状的方法。
• Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof
  申请人：Wu Xiaohua

  公开号：US10221168B1

  公开（公告）日：2019-03-05

  The present invention provides compounds that can enhance functional O-mannosylation of proteins including alpha-dystroglycan. Also provided are methods of preparation of the compounds defined by the formula I. Also provided are the methods of using the compounds or the pharmaceutical acceptable salts or prodrugs thereof in treating and preventing subjects suffering from the diseases including muscular dystrophies and cancers.

  本发明提供了一种可以增强蛋白质的O-甘露糖基化功能，包括α-骨骼肌糖蛋白的化合物。还提供了一种按照式I定义的化合物的制备方法。同时提供了使用这些化合物或其药用可接受的盐或前药来治疗和预防患有包括肌肉萎缩症和癌症在内的疾病的方法。
• BICYCLIC HETEROARLY ANALOGUES AS GPR119 MODULATORS
  申请人：Ye Xiang-Yang

  公开号：US20130053345A1

  公开（公告）日：2013-02-28

  Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, R 2 and R 4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  提供了结构式I的新化合物，或其对映体、顺反异构体、互变异构体、前药或盐，其中A、D、Di、E、J、L、n、Q、R2和R4在此定义，这些化合物是GPR119 G蛋白偶联受体调节剂。 GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病方面是有用的。因此，本公开还涉及包含这些新化合物的组合物以及使用任何这些新化合物或包含任何这些新化合物的组合物来治疗与GPR119 G蛋白偶联受体活性相关的疾病或病症的方法。
• Bicyclic heteroaryl compounds as GPR119 modulators
  申请人：Ye Xiang-Yang

  公开号：US08940716B2

  公开（公告）日：2015-01-27

  Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, R2 and R4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  本发明提供了结构式I的新化合物，或其对映异构体、非对映异构体、互变异构体、前药或其盐，其中A、D、Di、E、J、L、n、Q、R2和R4在此定义，这些化合物是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病方面是有用的。因此，本发明还涉及包含这些新化合物的组合物和使用任何这些新化合物或包含任何这些新化合物的组合物治疗与GPR119 G蛋白偶联受体活性相关的疾病或症状的方法。
• BICYCLIC HETEROARYL COMPOUNDS AS GPR119 MODULATORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2566860A1

  公开（公告）日：2013-03-13