methyl 5-[(tert-butyldimethylsilyloxy)methyl]isoxazole-3-carboxylate | 1219005-00-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 5-[(tert-butyldimethylsilyloxy)methyl]isoxazole-3-carboxylate
• 英文别名: Methyl 5-[[tert-butyl(dimethyl)silyl]oxymethyl]-1,2-oxazole-3-carboxylate
• CAS: 1219005-00-1
• 化学式: C₁₂H₂₁NO₄Si
• 分子量: 271.389
• InChiKey: KQXUULXBZMSQLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-[(tert-butyldimethylsilyloxy)methyl]isoxazole-3-carboxylate 在 盐酸羟胺 、 lithium methanolate 、 二异丁基氢化铝 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正庚烷 、 二氯甲烷 、 乙基苯 、 甲苯 为溶剂， 反应 32.5h， 生成 (2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-N,3-dihydroxy-2-methylpropanamide
  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：

  硝基乙酸甲酯 、 O-tert-butyldimethylsilylpropyn-3-ol 在 对苯二异氰酸酯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 192.0h， 以45%的产率得到methyl 5-[(tert-butyldimethylsilyloxy)methyl]isoxazole-3-carboxylate
  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

• [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
• Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC
  作者：Joseph S. Warmus、Cheryl L. Quinn、Clarke Taylor、Sean T. Murphy、Timothy A. Johnson、Chris Limberakis、Daniel Ortwine、Joel Bronstein、Paul Pagano、John D. Knafels、Sandra Lightle、Igor Mochalkin、Roger Brideau、Terry Podoll

  DOI：10.1016/j.bmcl.2012.01.140

  日期：2012.4

  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.