N-{[3-(4-chlorophenyl)-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl]acetyl}-L-alanine | 956188-57-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: N-{[3-(4-chlorophenyl)-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl]acetyl}-L-alanine
• 英文别名: (2S)-2-[[2-[3-(4-chlorophenyl)-5,9-dimethyl-7-oxofuro[3,2-g]chromen-6-yl]acetyl]amino]propanoic acid
• CAS: 956188-57-1
• 化学式: C₂₄H₂₀ClNO₆
• 分子量: 453.879
• InChiKey: BDYGEDWPWTXLIW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以86%的产率得到N-{[3-(4-chlorophenyl)-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl]acetyl}-L-alanine
  参考文献：
  名称：

  Antibiotic That Inhibits the ATPase Activity of an ATP-Binding Cassette Transporter by Binding to a Remote Extracellular Site

  摘要：

  Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics to treat resistant infections. In a high throughput screen (HTS) of 230 000 small molecules designed to identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into a small panel of potent compounds. We showed that these compounds target TarG, the transmembrane component of the two-component ATP-binding cassette (ABC) transporter TarGH, which exports WTA precursors to the cell surface for attachment to peptidoglycan. We purified, for the first time, a WTA transporter and have reconstituted ATPase activity in proteoliposomes.' We showed that this new compound series inhibits TarH-catalyzed ATP hydrolysis even though the binding site maps to TarG near the opposite side of the membrane. These are the first ABC transporter inhibitors shown to block ATPase activity by binding to the transmembrane domain. The compounds have potential as, therapeutic agents to treat S. aureus infections, and purification of the transmembrane transporter will enable further development.

  DOI：

  10.1021/jacs.7b04726

文献信息

• Antibiotic That Inhibits the ATPase Activity of an ATP-Binding Cassette Transporter by Binding to a Remote Extracellular Site
  作者：Leigh M. Matano、Heidi G. Morris、Anthony R. Hesser、Sara E. S. Martin、Wonsik Lee、Tristan W. Owens、Emaline Laney、Hidemasa Nakaminami、David Hooper、Timothy C. Meredith、Suzanne Walker

  DOI：10.1021/jacs.7b04726

  日期：2017.8.9

  Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics to treat resistant infections. In a high throughput screen (HTS) of 230 000 small molecules designed to identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into a small panel of potent compounds. We showed that these compounds target TarG, the transmembrane component of the two-component ATP-binding cassette (ABC) transporter TarGH, which exports WTA precursors to the cell surface for attachment to peptidoglycan. We purified, for the first time, a WTA transporter and have reconstituted ATPase activity in proteoliposomes.' We showed that this new compound series inhibits TarH-catalyzed ATP hydrolysis even though the binding site maps to TarG near the opposite side of the membrane. These are the first ABC transporter inhibitors shown to block ATPase activity by binding to the transmembrane domain. The compounds have potential as, therapeutic agents to treat S. aureus infections, and purification of the transmembrane transporter will enable further development.