methyl (2S)-2-(biphenyl-4-ylmethoxy)propanoate | 1219004-57-5

• 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: methyl (2S)-2-(biphenyl-4-ylmethoxy)propanoate
• 英文别名: methyl (2S)-2-[(4-phenylphenyl)methoxy]propanoate
• CAS: 1219004-57-5
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: YEPGWGXTPHNNGO-ZDUSSCGKSA-N

物化性质

• 沸点：
  401.0±33.0 °C(Predicted)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-(biphenyl-4-ylmethoxy)propanoate 在 正丁基锂 、 氯化亚砜 、 水 、 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 正庚烷 、 乙基苯 为溶剂， 反应 26.5h， 生成 (4S)-3-[(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-hydroxy-2-methylbutanoyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC

  摘要：

  Lipid A is an essential component of the Gram negative outer membrane, which protects the bacterium from attack of many antibiotics. The Lipid A biosynthesis pathway is essential for Gram negative bacterial growth and is unique to these bacteria. The first committed step in Lipid A biosynthesis is catalysis by LpxC, a zinc dependent deacetylase. We show the design of an LpxC inhibitor utilizing a robust model which directed efficient design of picomolar inhibitors. Analysis of physiochemical properties drove design to focus on an optimal lipophilicity profile. Further structure based design took advantage of a conserved water network over the active site, and with the optimal lipophilicity profile, led to an improved LpxC inhibitor with in vivo activity against wild type Pseudomonas aeruginosa. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.140
• 作为产物：
  描述：

  L-乳酸甲酯 、 4-溴甲基联苯 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 以85%的产率得到methyl (2S)-2-(biphenyl-4-ylmethoxy)propanoate
  参考文献：
  名称：

  Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC

  摘要：

  Lipid A is an essential component of the Gram negative outer membrane, which protects the bacterium from attack of many antibiotics. The Lipid A biosynthesis pathway is essential for Gram negative bacterial growth and is unique to these bacteria. The first committed step in Lipid A biosynthesis is catalysis by LpxC, a zinc dependent deacetylase. We show the design of an LpxC inhibitor utilizing a robust model which directed efficient design of picomolar inhibitors. Analysis of physiochemical properties drove design to focus on an optimal lipophilicity profile. Further structure based design took advantage of a conserved water network over the active site, and with the optimal lipophilicity profile, led to an improved LpxC inhibitor with in vivo activity against wild type Pseudomonas aeruginosa. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.140

文献信息

• Hydroxamic Acid Derivatives Useful as Antibacterial Agents
  申请人：Brown Matthew F.

  公开号：US20110178042A1

  公开（公告）日：2011-07-21

  The invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof, thereof, wherein: G is a group of formula (II); and pharmaceutically acceptable salts, prodrugs, hydrates, or solvates, thereof, wherein A, B. L 1 -L 4 A, B, R 1 -R 4 and m are as defined herein. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and their use in treating a bacterial infection.

  本发明涉及公式（I）的化合物或其药学上可接受的盐，其中：G是公式（II）的基团；以及其药学上可接受的盐、前药、水合物或溶剂化物，其中A、B、L1-L4、R1-R4和m的定义如本文所述。本发明还涉及包括公式（I）的化合物的药物组合物及其在治疗细菌感染中的应用。
• Hydroxamic Acid Derivatives Useful As Antibacterial Agents
  申请人：Pfizer Inc.

  公开号：US20140206651A1

  公开（公告）日：2014-07-24

  The invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof, thereof, wherein: G is a group of formula (II): and pharmaceutically acceptable salts, prodrugs, hydrates, or solvates, thereof, wherein A, B, L 1 -L 4 , A, B, R 1 -R 4 , and m are as defined herein. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and their use in treating a bacterial infection.

  本发明涉及式(I)的化合物：或其药学上可接受的盐，其中：G是式(II)的基团：以及其药学上可接受的盐、前药、水合物或溶剂化物，其中A、B、L1-L4、A、B、R1-R4和m的定义如本文所述。本发明还涉及包含式(I)化合物的制药组合物及其在治疗细菌感染中的应用。
• [EN] HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS<br/>[FR] DÉRIVÉS D'ACIDE HYDROXAMIQUE UTILES COMME AGENTS ANTIBACTÉRIENS
  申请人：PFIZER

  公开号：WO2010032147A3

  公开（公告）日：2010-06-03
• US8722686B2
  申请人：——

  公开号：US8722686B2

  公开（公告）日：2014-05-13
• US9340493B2
  申请人：——

  公开号：US9340493B2

  公开（公告）日：2016-05-17