5-(3,4-bis(benzyloxy)phenyl)-N-cyclopropylthiophene-2-carboxamide | 1067911-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-(3,4-bis(benzyloxy)phenyl)-N-cyclopropylthiophene-2-carboxamide
• 英文别名: 5-[3,4-bis(phenylmethoxy)phenyl]-N-cyclopropylthiophene-2-carboxamide
• CAS: 1067911-33-4
• 化学式: C₂₈H₂₅NO₃S
• 分子量: 455.577
• InChiKey: SHEPJOOJKBHISF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(3,4-bis(benzyloxy)phenyl)-N-cyclopropylthiophene-2-carboxamide 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以40%的产率得到N-cyclopropyl-5-(3,4-dihydroxyphenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Discovery of Inhibitors of Escherichia coli Methionine Aminopeptidase with the Fe(II)-Form Selectivity and Antibacterial Activity

  摘要：

  Methionine aminopeptidase (MetAP) is a promising target to develop novel antibiotics, because all bacteria express MetAP from a single gene that carries out the essential function of removing N-terminal methionine from nascent proteins. Divalent metal ions play a critical role in the catalysis, and there is an urgent need to define the actual metal used by MetAP in bacterial cells. By high throughput screening, we identified a novel class of catechol-containing MetAP inhibitors that display selectivity for the Fe(II)-form of MetAP. X-ray structure revealed that the inhibitor binds to MetAP at the active site with the catechol coordinating to the metal ions. Importantly, some of the inhibitors showed antibacterial activity at low micromolar concentration on Gram-positive and Gram-negative bacteria. Our data indicate that Fe(II) is the likely metal used by MetAP in the cellular environment, and MetAP inhibitors need to inhibit this metalloform of MetAP effectively to be therapeutically useful.

  DOI：

  10.1021/jm8005788
• 作为产物：
  描述：

  3,4-dibenzyloxyphenyl boronic acid 、 5-溴-N-环丙基-2-噻吩甲酰胺 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以60%的产率得到5-(3,4-bis(benzyloxy)phenyl)-N-cyclopropylthiophene-2-carboxamide
  参考文献：
  名称：

  Discovery of Inhibitors of Escherichia coli Methionine Aminopeptidase with the Fe(II)-Form Selectivity and Antibacterial Activity

  摘要：

  Methionine aminopeptidase (MetAP) is a promising target to develop novel antibiotics, because all bacteria express MetAP from a single gene that carries out the essential function of removing N-terminal methionine from nascent proteins. Divalent metal ions play a critical role in the catalysis, and there is an urgent need to define the actual metal used by MetAP in bacterial cells. By high throughput screening, we identified a novel class of catechol-containing MetAP inhibitors that display selectivity for the Fe(II)-form of MetAP. X-ray structure revealed that the inhibitor binds to MetAP at the active site with the catechol coordinating to the metal ions. Importantly, some of the inhibitors showed antibacterial activity at low micromolar concentration on Gram-positive and Gram-negative bacteria. Our data indicate that Fe(II) is the likely metal used by MetAP in the cellular environment, and MetAP inhibitors need to inhibit this metalloform of MetAP effectively to be therapeutically useful.

  DOI：

  10.1021/jm8005788

文献信息

• Discovery of Inhibitors of <i>Escherichia coli</i> Methionine Aminopeptidase with the Fe(II)-Form Selectivity and Antibacterial Activity
  作者：Wen-Long Wang、Sergio C. Chai、Min Huang、Hong-Zhen He、Thomas D. Hurley、Qi-Zhuang Ye

  DOI：10.1021/jm8005788

  日期：2008.10.9

  Methionine aminopeptidase (MetAP) is a promising target to develop novel antibiotics, because all bacteria express MetAP from a single gene that carries out the essential function of removing N-terminal methionine from nascent proteins. Divalent metal ions play a critical role in the catalysis, and there is an urgent need to define the actual metal used by MetAP in bacterial cells. By high throughput screening, we identified a novel class of catechol-containing MetAP inhibitors that display selectivity for the Fe(II)-form of MetAP. X-ray structure revealed that the inhibitor binds to MetAP at the active site with the catechol coordinating to the metal ions. Importantly, some of the inhibitors showed antibacterial activity at low micromolar concentration on Gram-positive and Gram-negative bacteria. Our data indicate that Fe(II) is the likely metal used by MetAP in the cellular environment, and MetAP inhibitors need to inhibit this metalloform of MetAP effectively to be therapeutically useful.