3-(2-amino-2-oxoethoxy)-1-benzothiophene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 3-(2-amino-2-oxoethoxy)-1-benzothiophene-2-carboxylic acid
• 英文别名: 3-(2-Amino-2-oxoethoxy)-1-benzothiophene-2-carboxylic acid
• 化学式: C₁₁H₉NO₄S
• 分子量: 251.263
• InChiKey: VZDQVFAOQBRANG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-(aminomethyl)phenyl)benzamide 、 3-(2-amino-2-oxoethoxy)-1-benzothiophene-2-carboxylic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以37.8%的产率得到N-(3-benzamidobenzyl)-3-(2-amino-2-oxoethoxy)benzothiophene-2-carboxamide
  参考文献：
  名称：

  Benzothiophene-2-carboxamide derivatives as SENPs inhibitors with selectivity within SENPs family

  摘要：

  The SUMO (small ubiquitin-related modifier)-specific proteases (SENPs) are responsible for the cleavage of SUMO from its target proteins, thus play important roles in the dynamic SUMOylation and deSU-MOylation processes. SENPs are related to a variety of human diseases including cancer and represent a new class of potential therapeutic targets with mechanism of action that is likely to be different from that of current clinically used drugs. However, potent inhibitors that are selective within the SENPs family members still remain a challenge due to their high homology. In order to demonstrate the feasibility of developing selective inhibitors within the SENPs family, we chose SENP1/2/5 as representatives, aiming to identify inhibitors with selectivity among the members. Starting from a hit compound ZCL951 from virtual screening, a series of benzothiophene-2-carboxamide inhibitors were designed based on the protein structures of SENP1, 2, and 5. First, an unoccupied hydrophobic pocket was first identified which led to IC50 as low as 0.56 mu M. Furthermore, the ethylacetate 77 gave both submicromolar inhibitory activity and 33-fold selectivity for SENP2 versus SENP5. They are the most potent and selective nonpeptidic inhibitor reported so far for the SENPs family, as far as we are aware. Their structure-activity relationship was also discussed. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112553
• 作为产物：
  描述：

  3-羟基苯并[B]噻吩-2-羧酸甲酯 在 lithium hydroxide monohydrate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3-(2-amino-2-oxoethoxy)-1-benzothiophene-2-carboxylic acid
  参考文献：
  名称：

  Benzothiophene-2-carboxamide derivatives as SENPs inhibitors with selectivity within SENPs family

  摘要：

  The SUMO (small ubiquitin-related modifier)-specific proteases (SENPs) are responsible for the cleavage of SUMO from its target proteins, thus play important roles in the dynamic SUMOylation and deSU-MOylation processes. SENPs are related to a variety of human diseases including cancer and represent a new class of potential therapeutic targets with mechanism of action that is likely to be different from that of current clinically used drugs. However, potent inhibitors that are selective within the SENPs family members still remain a challenge due to their high homology. In order to demonstrate the feasibility of developing selective inhibitors within the SENPs family, we chose SENP1/2/5 as representatives, aiming to identify inhibitors with selectivity among the members. Starting from a hit compound ZCL951 from virtual screening, a series of benzothiophene-2-carboxamide inhibitors were designed based on the protein structures of SENP1, 2, and 5. First, an unoccupied hydrophobic pocket was first identified which led to IC50 as low as 0.56 mu M. Furthermore, the ethylacetate 77 gave both submicromolar inhibitory activity and 33-fold selectivity for SENP2 versus SENP5. They are the most potent and selective nonpeptidic inhibitor reported so far for the SENPs family, as far as we are aware. Their structure-activity relationship was also discussed. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112553