2-((3R,6S)-3-(2-(2-aminoethylthio)acetamido)-2-hydroxy-1,2-oxaborinan-6-yl)acetic acid | 1360457-89-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-((3R,6S)-3-(2-(2-aminoethylthio)acetamido)-2-hydroxy-1,2-oxaborinan-6-yl)acetic acid
• 英文别名: 2-[(3R,6S)-3-[[2-(2-aminoethylsulfanyl)acetyl]amino]-2-hydroxyoxaborinan-6-yl]acetic acid
• CAS: 1360457-89-1
• 化学式: C₁₀H₁₉BN₂O₅S
• 分子量: 290.148
• InChiKey: QDDPUOLCDCSVML-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 2-((3R,6S)-3-(2-(2-aminoethylthio)acetamido)-2-hydroxy-1,2-oxaborinan-6-yl)acetic acid 、 2-[3-[[2-(2-Aminoethylsulfanyl)acetyl]amino]-2-hydroxyoxaborinan-6-yl]acetic acid
  参考文献：
  名称：

  Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases

  摘要：

  The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.

  DOI：

  10.1021/acs.jmedchem.5b00127