methyl (S)-2-([1,1'-biphenyl]-4-carboxamido)pent-4-ynoate

• 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 (S)-2-([1,1'-biphenyl]-4-carboxamido)pent-4-ynoate
• 英文别名: methyl (2S)-2-[(4-phenylbenzoyl)amino]pent-4-ynoate
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: KTBURPYKLYBTBT-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-([1,1'-biphenyl]-4-carboxamido)pent-4-ynoate 在 ammonium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 20.0h， 以100%的产率得到(S)-N-(1-(hydroxyamino)-1-oxopent-4-yn-2-yl)-[1,1'-biphenyl]-4-carboxamide
  参考文献：
  名称：

  Propargylglycine-based antimicrobial compounds are targets of TolC-dependent efflux systems in Escherichia coli

  摘要：

  A library of novel L-propargylglycine-based compounds were designed and synthesized with the goal of inhibiting the growth of Gram-negative bacteria by targeting LpxC, a highly conserved Gram-negative enzyme which performs an essential step in the lipid A biosynthetic pathway. These compounds were designed with and without a nucleoside and had varying tail structures, which modulate their lipophilicity. The synthetic scheme was improved compared to previous methods: a methyl ester intermediate was converted to a hydroxamic acid, which obviated the need for a THP protecting group and improved the yields and purity of the final compounds. Antimicrobial activity was observed for non-nucleoside compounds containing a phenyl propargyl ether tail (5) or a biphenyl tail (6). An MIC of 16 mu g/mL was achieved for 6 in Escherichia coli, but inhibition was only possible in the absence of TolC-mediated efflux. Compound 5 had an initial MIC > 160 mu g/mL in E. coli. Enhancing outer membrane permeability or eliminating efflux reduced the MIC modestly to 100 mu g/mL and 80 mu g/mL, respectively. These results highlight the importance of hydrophobicity of this class of compounds in developing LpxC inhibitors, as well as the design challenge of avoiding multidrug efflux activity.

  DOI：

  10.1016/j.bmcl.2019.126875
• 作为产物：
  描述：

  (2S)-2-[[叔丁氧羰基]氨基]-4-戊炔酸酸甲酯 在 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 methyl (S)-2-([1,1'-biphenyl]-4-carboxamido)pent-4-ynoate
  参考文献：
  名称：

  Propargylglycine-based antimicrobial compounds are targets of TolC-dependent efflux systems in Escherichia coli

  摘要：

  A library of novel L-propargylglycine-based compounds were designed and synthesized with the goal of inhibiting the growth of Gram-negative bacteria by targeting LpxC, a highly conserved Gram-negative enzyme which performs an essential step in the lipid A biosynthetic pathway. These compounds were designed with and without a nucleoside and had varying tail structures, which modulate their lipophilicity. The synthetic scheme was improved compared to previous methods: a methyl ester intermediate was converted to a hydroxamic acid, which obviated the need for a THP protecting group and improved the yields and purity of the final compounds. Antimicrobial activity was observed for non-nucleoside compounds containing a phenyl propargyl ether tail (5) or a biphenyl tail (6). An MIC of 16 mu g/mL was achieved for 6 in Escherichia coli, but inhibition was only possible in the absence of TolC-mediated efflux. Compound 5 had an initial MIC > 160 mu g/mL in E. coli. Enhancing outer membrane permeability or eliminating efflux reduced the MIC modestly to 100 mu g/mL and 80 mu g/mL, respectively. These results highlight the importance of hydrophobicity of this class of compounds in developing LpxC inhibitors, as well as the design challenge of avoiding multidrug efflux activity.

  DOI：

  10.1016/j.bmcl.2019.126875