(R)-dimethyl 2-(4-((3-formylphenoxy)methyl)benzamido)pentanedioate | 1346225-77-1

• 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)-dimethyl 2-(4-((3-formylphenoxy)methyl)benzamido)pentanedioate
• 英文别名: dimethyl (2R)-2-[[4-[(3-formylphenoxy)methyl]benzoyl]amino]pentanedioate
• CAS: 1346225-77-1
• 化学式: C₂₂H₂₃NO₇
• 分子量: 413.427
• InChiKey: MOJMRFWZGIDSKJ-LJQANCHMSA-N

物化性质

• 熔点：
  84-87 °C
• 沸点：
  616.6±55.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-dimethyl 2-(4-((3-formylphenoxy)methyl)benzamido)pentanedioate 在 哌啶 、 溶剂黄146 、 lithium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 0.67h， 生成 (R,Z)-2-(4-((3-((4-oxo-2-thioxothiazolidin-5-ylidene)methyl)phenoxy)methyl)benzamido)pentanedioic acid
  参考文献：
  名称：

  New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation

  摘要：

  Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC50 values up to 28 mu M. Inhibitor 37, with an IC50 of 34 mu M, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 mu g/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.017
• 作为产物：
  描述：

  methyl 4-((3-formylphenoxy)methyl)benzoate 在 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (R)-dimethyl 2-(4-((3-formylphenoxy)methyl)benzamido)pentanedioate
  参考文献：
  名称：

  New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation

  摘要：

  Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC50 values up to 28 mu M. Inhibitor 37, with an IC50 of 34 mu M, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 mu g/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.017

文献信息

• New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation
  作者：Nace Zidar、Tihomir Tomašić、Roman Šink、Andreja Kovač、Delphine Patin、Didier Blanot、Carlos Contreras-Martel、Andréa Dessen、Manica Müller Premru、Anamarija Zega、Stanislav Gobec、Lucija Peterlin Mašič、Danijel Kikelj

  DOI：10.1016/j.ejmech.2011.09.017

  日期：2011.11

  Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC50 values up to 28 mu M. Inhibitor 37, with an IC50 of 34 mu M, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 mu g/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. (C) 2011 Elsevier Masson SAS. All rights reserved.