2-(5-(bromomethyl)benzo[b]thiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | 1007551-72-5

• 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: 2-(5-(bromomethyl)benzo[b]thiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• 英文别名: pinacol 5-bromomethylbenzo[b]thiophen-2-ylboronate；2-[5-(Bromomethyl)-1-benzothiophen-2-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 1007551-72-5
• 化学式: C₁₅H₁₈BBrO₂S
• 分子量: 353.088
• InChiKey: DJNGUNABKZEUOB-UHFFFAOYSA-N

物化性质

• 沸点：
  444.6±30.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-(bromomethyl)benzo[b]thiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 在 potassium iodide 水 作用下， 以 丙酮 为溶剂， 反应 1.0h， 以80%的产率得到5-hydroxymethylbenzo[b]thiophen-2-ylboronic acid
  参考文献：
  名称：

  Optimizing Cell Permeation of an Antibiotic Resistance Inhibitor for Improved Efficacy

  摘要：

  Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.

  DOI：

  10.1021/jm070643q
• 作为产物：
  描述：

  5-甲基-2-(4,4,5,5-四甲基-1,3,2-二氧硼杂环戊烷-2-基)-苯并[b]噻吩 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 以62%的产率得到2-(5-(bromomethyl)benzo[b]thiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
  参考文献：
  名称：

  Optimizing Cell Permeation of an Antibiotic Resistance Inhibitor for Improved Efficacy

  摘要：

  Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.

  DOI：

  10.1021/jm070643q

文献信息

• Optimizing Cell Permeation of an Antibiotic Resistance Inhibitor for Improved Efficacy
  作者：Alberto Venturelli、Donatella Tondi、Laura Cancian、Federica Morandi、Giuseppe Cannazza、Bernardetta Segatore、Fabio Prati、Gianfranco Amicosante、Brian K. Shoichet、M. Paola Costi

  DOI：10.1021/jm070643q

  日期：2007.11.1

  Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.