(R)-N-hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide | 1548043-54-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-N-hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide
• 英文别名: N-hydroxy-2-[(1R)-2-hydroxy-1-[4-(2-phenylethynyl)phenyl]ethoxy]acetamide
• CAS: 1548043-54-4
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: TUDHZAYBRVJBOP-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-5-[4-(phenylethynyl)phenyl]-1,4-dioxan-2-one 在 盐酸羟胺 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以56%的产率得到(R)-N-hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular docking studies of benzyloxyacetohydroxamic acids as LpxC inhibitors

  摘要：

  The inhibition of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represents a promising strategy to combat infections caused by multidrug-resistant Gram-negative bacteria. In order to elucidate the functional groups being important for the inhibition of LpxC, the structure of our previously reported hydroxamic acid 4 should be systematically varied. Therefore, a series of benzyloxyacetohydroxamic acids was prepared, of which the diphenylacetylene derivatives 28 (K-i = 95 nM) and 21 (K-i = 66 nM) were the most potent inhibitors of Escherichia coli LpxC. These compounds could be synthesized in a stereoselective manner employing a Sharpless asymmetric dihydroxylation and a Sonogashira coupling in the key steps. The obtained structure-activity relationships could be rationalized by molecular docking studies. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.057

文献信息

• Synthesis, biological evaluation and molecular docking studies of benzyloxyacetohydroxamic acids as LpxC inhibitors
  作者：Marina Szermerski、Jelena Melesina、Kanin Wichapong、Marius Löppenberg、Joachim Jose、Wolfgang Sippl、Ralph Holl

  DOI：10.1016/j.bmc.2013.12.057

  日期：2014.2

  The inhibition of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represents a promising strategy to combat infections caused by multidrug-resistant Gram-negative bacteria. In order to elucidate the functional groups being important for the inhibition of LpxC, the structure of our previously reported hydroxamic acid 4 should be systematically varied. Therefore, a series of benzyloxyacetohydroxamic acids was prepared, of which the diphenylacetylene derivatives 28 (K-i = 95 nM) and 21 (K-i = 66 nM) were the most potent inhibitors of Escherichia coli LpxC. These compounds could be synthesized in a stereoselective manner employing a Sharpless asymmetric dihydroxylation and a Sonogashira coupling in the key steps. The obtained structure-activity relationships could be rationalized by molecular docking studies. (C) 2013 Elsevier Ltd. All rights reserved.