2-(4-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid | 1195960-97-4

• 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: 2-(4-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid
• 英文别名: 2-(4-((5-(3,4-Dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid；2-[4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-sulfanylideneimidazolidin-1-yl]-3-phenylpropanoic acid
• CAS: 1195960-97-4
• 化学式: C₂₃H₁₆Cl₂N₂O₄S
• 分子量: 487.363
• InChiKey: CZUADNIMRCRNSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid 在 氯化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以48%的产率得到2-(4-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanamide
  参考文献：
  名称：

  Discovery of Novel Putative Inhibitors of UDP-GlcNAc 2-Epimerase as Potent Antibacterial Agents

  摘要：

  We present the discovery and optimization of a novel series of inhibitors of bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this letter). Starting from virtual screening hits, the activity of various inhibitory molecules was optimized using a combination of structure-based and rational design approaches. We successfully designed and identified a 2-epimerase inhibitor (compound 12-ES-Na, that we named Epimerox), which blocked the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.9 mu M MIC (minimum inhibitory concentration) and showed potent broad range activity against all Gram-positive bacteria that were tested. Additionally a microplate coupled assay was performed to further confirm that the 2-epimerase inhibition of Epimerox was through a target specific mechanism. Furthermore, Epimerox demonstrated in vivo efficacy and had a pharmacokinetic profile that is consonant with it being developed into a promising new antibiotic agent for treatment of infections caused by Gram-positive bacteria.

  DOI：

  10.1021/ml4001936
• 作为产物：
  描述：

  glycylphenylalanine 在 β-丙氨酸 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 2-(4-((5-(3,4-dichlorophenyl)furan-2-yl)methylene)-5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid
  参考文献：
  名称：

  Oxo-Imidazolyl Compounds

  摘要：

  由化学式I和II代表的化合物，或其药用可接受的盐：抑制细菌2-表皮酶，是有用的抗感染剂。

  公开号：

  US20090298900A1

文献信息

• Oxo-Imidazolyl Compounds
  申请人：Bearss David J.

  公开号：US20090298900A1

  公开（公告）日：2009-12-03

  Compounds represented by Formula I and II, or pharmaceutically acceptable salts thereof: inhibit bacterial 2-epimerase and are useful anti-infective agents.

  由化学式I和II代表的化合物，或其药用可接受的盐：抑制细菌2-表皮酶，是有用的抗感染剂。
• Oxo-imidazolyl compounds
  申请人：Bearss David J.

  公开号：US08759384B2

  公开（公告）日：2014-06-24

  Compounds represented by Formula I and II, or pharmaceutically acceptable salts thereof: inhibit bacterial 2-epimerase and are useful anti-infective agents.

  公式I和II所代表的化合物，或其药学上可接受的盐：抑制细菌2-表异构酶并且是有用的抗感染剂。
• Discovery of Novel Putative Inhibitors of UDP-GlcNAc 2-Epimerase as Potent Antibacterial Agents
  作者：Yong Xu、Benjamin Brenning、Adrianne Clifford、David Vollmer、Jared Bearss、Carissa Jones、Virgil McCarthy、Chongtie Shi、Bradley Wolfe、Bhasker Aavula、Steve Warner、David J. Bearss、Michael V. McCullar、Raymond Schuch、Adam Pelzek、Shyam S. Bhaskaran、C. Erec Stebbins、Allan R. Goldberg、Vincent A. Fischetti、Hariprasad Vankayalapati

  DOI：10.1021/ml4001936

  日期：2013.12.12

  We present the discovery and optimization of a novel series of inhibitors of bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this letter). Starting from virtual screening hits, the activity of various inhibitory molecules was optimized using a combination of structure-based and rational design approaches. We successfully designed and identified a 2-epimerase inhibitor (compound 12-ES-Na, that we named Epimerox), which blocked the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.9 mu M MIC (minimum inhibitory concentration) and showed potent broad range activity against all Gram-positive bacteria that were tested. Additionally a microplate coupled assay was performed to further confirm that the 2-epimerase inhibition of Epimerox was through a target specific mechanism. Furthermore, Epimerox demonstrated in vivo efficacy and had a pharmacokinetic profile that is consonant with it being developed into a promising new antibiotic agent for treatment of infections caused by Gram-positive bacteria.