methyl 3-(4-benzoylphenylamino)-3-oxopropanoate | 1233345-50-0

• 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 3-(4-benzoylphenylamino)-3-oxopropanoate
• 英文别名: Methyl 3-(4-benzoylanilino)-3-oxopropanoate；methyl 3-(4-benzoylanilino)-3-oxopropanoate
• CAS: 1233345-50-0
• 化学式: C₁₇H₁₅NO₄
• 分子量: 297.31
• InChiKey: BDPQORZEVOWERJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-benzoylphenylamino)-3-oxopropanoate 在 sodium ethanolate 、 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 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.0h， 生成 N-(4-benzoylphenyl)-4-hydroxy-2-oxo-5-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Biophysical Investigation of the Mode of Inhibition of Tetramic Acids, the Allosteric Inhibitors of Undecaprenyl Pyrophosphate Synthase

  摘要：

  Undecaprenyl pyrophosphate synthase (U PPS) catalyzes the consecutive condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to generate the C-55 undecaprenyl pyrophosphate (UPP). It has been demonstrated that tetramic acids (TAs) are selective and potent inhibitors of U PPS, but the mode of inhibition was unclear. In this work, we used a fluorescent FPP probe to study possible TA binding at the FPP binding site. A photosensitive TA analogue was designed and synthesized for the study of the site of interaction of TA with UPPS using photo-cross-linking and mass spectrometry. The interaction of substrates with UPPS and with the UPPS center dot TA complex was investigated by protein fluorescence spectroscopy. Our results suggested that tetramic acid binds to U PPS at an allosteric site adjacent to the FPP binding site. TA binds to free UPPS enzyme but not to substrate-bound UPPS. Unlike Escherichia coli UPPS which follows an ordered substrate binding mechanism, Streptococcus pneumoniae UPPS appears to follow a random-sequential substrate binding mechanism. Only one substrate, FPP or IPP, is able to bind to the UPPS center dot TA complex, but the quaternary complex, UPPS center dot TA center dot FPP center dot IPP, cannot be formed. We propose that binding of TA to UPPS significantly alters the conformation of UPPS needed for proper substrate binding. As the result, substrate turnover is prevented, leading to the inhibition of UPPS catalytic activity. These probe compounds and biophysical assays also allowed its to quickly study the mode of inhibition of other UPPS inhibitors identified from a high-throughput screening and inhibitors produced from a medicinal chemistry program.

  DOI：

  10.1021/bi100523c
• 作为产物：
  描述：

  丙二酸甲酯酰氯 、 4-氨基二苯甲酮 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 以56%的产率得到methyl 3-(4-benzoylphenylamino)-3-oxopropanoate
  参考文献：
  名称：

  Biophysical Investigation of the Mode of Inhibition of Tetramic Acids, the Allosteric Inhibitors of Undecaprenyl Pyrophosphate Synthase

  摘要：

  Undecaprenyl pyrophosphate synthase (U PPS) catalyzes the consecutive condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to generate the C-55 undecaprenyl pyrophosphate (UPP). It has been demonstrated that tetramic acids (TAs) are selective and potent inhibitors of U PPS, but the mode of inhibition was unclear. In this work, we used a fluorescent FPP probe to study possible TA binding at the FPP binding site. A photosensitive TA analogue was designed and synthesized for the study of the site of interaction of TA with UPPS using photo-cross-linking and mass spectrometry. The interaction of substrates with UPPS and with the UPPS center dot TA complex was investigated by protein fluorescence spectroscopy. Our results suggested that tetramic acid binds to U PPS at an allosteric site adjacent to the FPP binding site. TA binds to free UPPS enzyme but not to substrate-bound UPPS. Unlike Escherichia coli UPPS which follows an ordered substrate binding mechanism, Streptococcus pneumoniae UPPS appears to follow a random-sequential substrate binding mechanism. Only one substrate, FPP or IPP, is able to bind to the UPPS center dot TA complex, but the quaternary complex, UPPS center dot TA center dot FPP center dot IPP, cannot be formed. We propose that binding of TA to UPPS significantly alters the conformation of UPPS needed for proper substrate binding. As the result, substrate turnover is prevented, leading to the inhibition of UPPS catalytic activity. These probe compounds and biophysical assays also allowed its to quickly study the mode of inhibition of other UPPS inhibitors identified from a high-throughput screening and inhibitors produced from a medicinal chemistry program.

  DOI：

  10.1021/bi100523c

文献信息

• Biophysical Investigation of the Mode of Inhibition of Tetramic Acids, the Allosteric Inhibitors of Undecaprenyl Pyrophosphate Synthase
  作者：Lac V. Lee、Brian Granda、Karl Dean、Jianshi Tao、Eugene Liu、Rui Zhang、Stefan Peukert、Sompong Wattanasin、Xiaoling Xie、Neil S. Ryder、Ruben Tommasi、Gejing Deng

  DOI：10.1021/bi100523c

  日期：2010.6.29

  Undecaprenyl pyrophosphate synthase (U PPS) catalyzes the consecutive condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to generate the C-55 undecaprenyl pyrophosphate (UPP). It has been demonstrated that tetramic acids (TAs) are selective and potent inhibitors of U PPS, but the mode of inhibition was unclear. In this work, we used a fluorescent FPP probe to study possible TA binding at the FPP binding site. A photosensitive TA analogue was designed and synthesized for the study of the site of interaction of TA with UPPS using photo-cross-linking and mass spectrometry. The interaction of substrates with UPPS and with the UPPS center dot TA complex was investigated by protein fluorescence spectroscopy. Our results suggested that tetramic acid binds to U PPS at an allosteric site adjacent to the FPP binding site. TA binds to free UPPS enzyme but not to substrate-bound UPPS. Unlike Escherichia coli UPPS which follows an ordered substrate binding mechanism, Streptococcus pneumoniae UPPS appears to follow a random-sequential substrate binding mechanism. Only one substrate, FPP or IPP, is able to bind to the UPPS center dot TA complex, but the quaternary complex, UPPS center dot TA center dot FPP center dot IPP, cannot be formed. We propose that binding of TA to UPPS significantly alters the conformation of UPPS needed for proper substrate binding. As the result, substrate turnover is prevented, leading to the inhibition of UPPS catalytic activity. These probe compounds and biophysical assays also allowed its to quickly study the mode of inhibition of other UPPS inhibitors identified from a high-throughput screening and inhibitors produced from a medicinal chemistry program.