2-{4-[3-Methyl-1-(1-thiophen-2-ylmethyl-1H-tetrazol-5-yl)-butyl]-piperazin-1-yl}-benzothiazole

• 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: 2-{4-[3-Methyl-1-(1-thiophen-2-ylmethyl-1H-tetrazol-5-yl)-butyl]-piperazin-1-yl}-benzothiazole
• 英文别名: 2-[4-[3-methyl-1-[1-(thiophen-2-ylmethyl)tetrazol-5-yl]butyl]piperazin-1-yl]-1,3-benzothiazole
• 化学式: C₂₂H₂₇N₇S₂
• 分子量: 453.635
• InChiKey: NKRKVGQWHSMKTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯苯并噻唑 在 copper(l) iodide 、 苄基三乙基氯化铵 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 36.5h， 生成 2-{4-[3-Methyl-1-(1-thiophen-2-ylmethyl-1H-tetrazol-5-yl)-butyl]-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

文献信息

• Small molecules enhance functional O-mannosylation of Alpha-dystroglycan
  作者：Fengping Lv、Zhi-fang Li、Wenhao Hu、Xiaohua Wu

  DOI：10.1016/j.bmc.2015.11.011

  日期：2015.12

  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.