L 161,240

• 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: L 161,240
• 英文别名: (4r)-2-(3,4-Dimethoxy-5-Propylphenyl)-N-Hydroxy-4,5-Dihydro-1,3-Oxazole-4-Carboxamide
• 化学式: C₁₅H₂₀N₂O₅
• 分子量: 308.334
• InChiKey: DGGKRIGJIQRXQD-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  89.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[(R)-1-(2,4-Dimethoxy-benzyloxycarbamoyl)-2-hydroxy-ethyl]-3,4-dimethoxy-5-propyl-benzamide 在 吡啶 、 二甲基乙基硅烷 、 polystyrene tosyl chloride resin 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 L 161,240
  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

• ETHYNYLBENZENE DERIVATIVES
  申请人：Zhou Pei

  公开号：US20130231323A1

  公开（公告）日：2013-09-05

  Disclosed are compounds of formulae (I), (II), and (II)I: and pharmaceutically acceptable salts thereof, wherein the variables, R, R 1 , R 2 , R 3 , R 101 , L, D, Q, Y, X, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.

  本发明涉及式(I)、(II)和(II)I的化合物及其药学上可接受的盐，其中变量R、R1、R2、R3、R101、L、D、Q、Y、X和Z的定义如下。这些化合物可用于治疗革兰氏阴性菌感染。
• 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.
• Ethynylbenzene Derivatives
  申请人：Duke University

  公开号：US20170349544A1

  公开（公告）日：2017-12-07

  Disclosed are compounds of formulae (I), (II), and (II)I: and pharmaceutically acceptable salts thereof, wherein the variables, R, R 1 , R 2 , R 3 , R 101 , L, D, Q, Y, X, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.
• US9738604B2
  申请人：——

  公开号：US9738604B2

  公开（公告）日：2017-08-22
• High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of <i>Escherichia </i><i>c</i><i>oli</i> LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties
  作者：Michael C. Pirrung、L. Nathan Tumey、Amanda L. McClerren、Christian R. H. Raetz

  DOI：10.1021/ja0209114

  日期：2003.2.1

  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.