(6R,7R)-4-methoxybenzyl 3-(((4-methyl-2-oxo-2H-chromen-7-yl)thio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide | 1450821-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (6R,7R)-4-methoxybenzyl 3-(((4-methyl-2-oxo-2H-chromen-7-yl)thio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide
• 英文别名: (4-methoxyphenyl)methyl (6R,7R)-3-[(4-methyl-2-oxochromen-7-yl)sulfanylmethyl]-5,8-dioxo-7-[(2-phenylacetyl)amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；(4-methoxyphenyl)methyl (6R,7R)-3-[(4-methyl-2-oxochromen-7-yl)sulfanylmethyl]-5,8-dioxo-7-[(2-phenylacetyl)amino]-5λ4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 1450821-69-8
• 化学式: C₃₄H₃₀N₂O₈S₂
• 分子量: 658.753
• InChiKey: AKNYJBHWCNXTOZ-BPHZTKSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  173
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (6R,7R)-4-methoxybenzyl 3-(((4-methyl-2-oxo-2H-chromen-7-yl)thio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide 在 苯甲醚 、 三氟乙酸 作用下， 以88%的产率得到(6R,7R)-3-(((4-methyl-2-oxo-2H-chromen-7-yl)thio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 5-oxide
  参考文献：
  名称：

  Assay Platform for Clinically Relevant Metallo-β-lactamases

  摘要：

  Metallo-beta-lactamases (MBLs) are a growing threat to the use of almost all clinically used beta-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-beta-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (Sao Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic,substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4- chloroisoquinolinols as potential pan MBL inhibitors.

  DOI：

  10.1021/jm400769b
• 作为产物：
  描述：

  7-苯乙酰氨基-3-氯甲基-4-头孢烷酸对甲氧基苄酯 在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (6R,7R)-4-methoxybenzyl 3-(((4-methyl-2-oxo-2H-chromen-7-yl)thio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide
  参考文献：
  名称：

  Assay Platform for Clinically Relevant Metallo-β-lactamases

  摘要：

  Metallo-beta-lactamases (MBLs) are a growing threat to the use of almost all clinically used beta-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-beta-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (Sao Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic,substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4- chloroisoquinolinols as potential pan MBL inhibitors.

  DOI：

  10.1021/jm400769b

文献信息

• Assay Platform for Clinically Relevant Metallo-β-lactamases
  作者：Sander S. van Berkel、Jürgen Brem、Anna M. Rydzik、Ramya Salimraj、Ricky Cain、Anil Verma、Raymond J. Owens、Colin W. G. Fishwick、James Spencer、Christopher J. Schofield

  DOI：10.1021/jm400769b

  日期：2013.9.12

  Metallo-beta-lactamases (MBLs) are a growing threat to the use of almost all clinically used beta-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-beta-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (Sao Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic,substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4- chloroisoquinolinols as potential pan MBL inhibitors.