(R)-2-(4-Methoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-(4-Methoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide
• 英文别名: (4R)-N-hydroxy-2-(4-methoxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide
• 化学式: C₁₁H₁₂N₂O₄
• 分子量: 236.227
• InChiKey: PXLIHBHOMKQEJN-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-2-(4-Methoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid (2,4-dimethoxy-benzyloxy)-amide 在 二甲基乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (R)-2-(4-Methoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide
  参考文献：
  名称：

  High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of Escherichia coli LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties

  摘要：

  LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wildtype Pseudomonas aeruginosa. Inhibition of the E coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.

  DOI：

  10.1021/ja0209114

文献信息

• Carbohydroxamido-oxazolidines: antibacterial agents that target lipid A biosynthesis
  作者：Meng-Hsin Chen、Mark G. Steiner、Stephen E. de Laszlo、Arthur A. Patchett、Matt S. Anderson、Sheryl A. Hyland、H. Russell Onishi、Lynn L. Silyer、Christian R.H. Raetz

  DOI：10.1016/s0960-894x(98)00749-5

  日期：1999.2

  A series of carbohydroxamido-oxazolidine inhibitors of UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase, the enzyme responsible for the second step in lipid A biosynthesis, was identified. The most potent analog L-161,240 showed an IC50 = 30 nM in the DEACET assay and displayed an MIC of 1-3 mu g/mL against wild-type E. coli. (C) 1999 Elsevier Science Ltd. All rights reserved.
• ANTIBACTERIAL COMPOSITIONS
  申请人：Patten Phillip A.

  公开号：US20120283175A1

  公开（公告）日：2012-11-08

  The present invention provides a methods and pharmaceutical compositions useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, a synergistic combination of an inhibitor of LpxC and second antibacterial agent.