1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione | 165663-10-5

• 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: 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione
• CAS: 165663-10-5
• 化学式: C₁₅H₁₀Cl₂N₂O₂
• 分子量: 321.163
• InChiKey: OOCOGUZUPHKGOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione 在 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 15.0h， 生成 1,2-bis(4-chlorophenyl)-5-hydroxy-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylic acid (4-hydroxyphenyl)amide
  参考文献：
  名称：

  Pyrazolidine-3,5-diones and 5-Hydroxy-1H-pyrazol-3(2H)-ones, Inhibitors of UDP-N-acetylenolpyruvyl Glucosamine Reductase

  摘要：

  A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)ones show low micromolar IC50 values versus E. coli MurB and submicromolar minimal inhibitory concentrations ( MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site.

  DOI：

  10.1021/jm060499t
• 作为产物：
  描述：

  (E)-Bis(4-chlorophenyl)diazene 在 sodium ethanolate 、 氯化铵 、 锌 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 9.5h， 生成 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione
  参考文献：
  名称：

  Pyrazolidine-3,5-diones and 5-Hydroxy-1H-pyrazol-3(2H)-ones, Inhibitors of UDP-N-acetylenolpyruvyl Glucosamine Reductase

  摘要：

  A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)ones show low micromolar IC50 values versus E. coli MurB and submicromolar minimal inhibitory concentrations ( MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site.

  DOI：

  10.1021/jm060499t

文献信息

• Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives
  作者：Xu-Yao Zhang、Yi-Fei Gu、Ting Chen、Dong-Xiao Yang、Xi-Xin Wang、Bai-Ling Jiang、Kun-Peng Shao、Wen Zhao、Cong Wang、Jun-Wei Wang、Qiu-Rong Zhang、Hong-Min Liu

  DOI：10.1039/c5md00240k

  日期：——

  To develop potent and selective anticancer agents, a series of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives were designed and synthesized.

  为了开发有效和选择性的抗癌药物，设计并合成了一系列新型的4-取代1,2-双(4-氯苯基)-吡唑啉-3,5-二酮衍生物。
• 3,5-Dioxopyrazolidines, Novel Inhibitors of UDP- <i>N</i> - Acetylenolpyruvylglucosamine Reductase (MurB) with Activity against Gram-Positive Bacteria
  作者：Youjun Yang、Anatoly Severin、Rajiv Chopra、Girija Krishnamurthy、Guy Singh、William Hu、David Keeney、Kristine Svenson、Peter J. Petersen、Pornpen Labthavikul、David M. Shlaes、Beth A. Rasmussen、Amedeo A. Failli、Jay S. Shumsky、Kristina M. K. Kutterer、Adam Gilbert、Tarek S. Mansour

  DOI：10.1128/aac.50.2.556-564.2006

  日期：2006.2

  A series of 3,5-dioxopyrazolidines was identified as novel inhibitors of UDP- N -acetylenolpyruvylglucosamine reductase (MurB). Compounds 1 to 3, which are 1,2-bis(4-chlorophenyl)-3,5-dioxopyrazolidine-4-carboxamides, inhibited Escherichia coli MurB, Staphyloccocus aureus MurB, and E. coli MurA with 50% inhibitory concentrations (IC ₅₀ s) in the range of 4.1 to 6.8 μM, 4.3 to 10.3 μM, and 6.8 to 29.4 μM, respectively. Compound 4, a C-4-unsubstituted 1,2-bis(3,4-dichlorophenyl)-3,5-dioxopyrazolidine, showed moderate inhibitory activity against E. coli MurB, S. aureus MurB, and E. coli MurC (IC ₅₀ s, 24.5 to 35 μM). A fluorescence-binding assay indicated tight binding of compound 3 with E. coli MurB, giving a dissociation constant of 260 nM. Structural characterization of E. coli MurB was undertaken, and the crystal structure of a complex with compound 4 was obtained at 2.4 Å resolution. The crystal structure indicated the binding of a compound at the active site of MurB and specific interactions with active-site residues and the bound flavin adenine dinucleotide cofactor. Peptidoglycan biosynthesis studies using a strain of Staphylococcus epidermidis revealed reduced peptidoglycan biosynthesis upon incubation with 3,5-dioxopyrazolidines, with IC ₅₀ s of 0.39 to 11.1 μM. Antibacterial activity was observed for compounds 1 to 3 (MICs, 0.25 to 16 μg/ml) and 4 (MICs, 4 to 8 μg/ml) against gram-positive bacteria including methicillin-resistant S. aureus , vancomycin-resistant Enterococcus faecalis , and penicillin-resistant Streptococcus pneumoniae .

  摘要 一系列 3,5-二氧代吡唑烷类化合物被鉴定为 UDP-N-甲基吡咯烷酮的新型抑制剂。 N -乙酰苯酚丙酮酰葡糖胺还原酶 (MurB) 的新型抑制剂。化合物 1 至 3 均为 1,2-双（4-氯苯基）-3,5-二氧代吡唑烷-4-甲酰胺类化合物，可抑制 大肠杆菌 金黄色葡萄球菌 金黄色葡萄球菌 和 大肠杆菌 MurA 的 50%抑制浓度（IC 50 范围分别为 4.1 至 6.8 μM、4.3 至 10.3 μM 和 6.8 至 29.4 μM。化合物 4 是一种 C-4 未取代的 1,2-双（3,4-二氯苯基）-3,5-二氧代吡唑烷，对大肠杆菌和大肠埃希氏菌表现出中等程度的抑制活性。 大肠杆菌 金黄色葡萄球菌 金黄色葡萄球菌 MurB 和 大肠杆菌 MurC（IC 50 s，24.5 至 35 μM）。荧光结合试验表明化合物 3 与大肠杆菌 MurB 和 MurC（IC 50 秒，24.5 至 35 μM）紧密结合。 大肠杆菌 MurB 的紧密结合，解离常数为 260 nM。大肠杆菌 MurB 的结构特征 大肠杆菌 MurB 的结构表征，并获得了与化合物 4 复合物的晶体结构，分辨率为 2.4 Å。晶体结构表明，化合物与 MurB 的活性位点结合，并与活性位点残基和结合的黄素腺嘌呤二核苷酸辅助因子发生了特异性相互作用。使用一株表皮葡萄球菌进行肽聚糖生物合成研究。 表皮葡萄球菌 发现，在与 3,5-二氧代吡唑烷类化合物培养后，肽聚糖的生物合成减少，IC 50 为 0.39 至 11.1 μM。化合物 1 至 3（MICs 为 0.25 至 16 μg/ml）和化合物 4（MICs 为 4 至 8 μg/ml）对革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌）具有抗菌活性。 金黄色葡萄球菌 耐万古霉素 耐万古霉素 耐青霉素肺炎链球菌 肺炎链球菌 .
• 4-Alkyl and 4,4′-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives as new inhibitors of bacterial cell wall biosynthesis
  作者：Kristina M.K. Kutterer、Jamie M. Davis、Guy Singh、Youjun Yang、William Hu、Anatoly Severin、Beth A. Rasmussen、Girija Krishnamurthy、Amedeo Failli、Alan H. Katz

  DOI：10.1016/j.bmcl.2005.03.058

  日期：2005.5

  Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against Gram-positive bacteria, particularly penicillin-resistant Streptococcus pneumoniae (PRSP). Derivative 71 demonstrated antibacterial activity against both Gram-positive and Gram-negative bacteria. Derivatives 7f and 10a also demonstrated potent nanomolar K(d) values in their binding to MurB. (c) 2005 Elsevier Ltd. All rights reserved.
• Pyrazolidine-3,5-diones and 5-Hydroxy-1<i>H</i>-pyrazol-3(2<i>H</i>)-ones, Inhibitors of UDP-<i>N</i>-acetylenolpyruvyl Glucosamine Reductase
  作者：Adam M. Gilbert、Amedeo Failli、Jay Shumsky、Youjun Yang、Anatoly Severin、Guy Singh、William Hu、David Keeney、Peter J. Petersen、Alan H. Katz

  DOI：10.1021/jm060499t

  日期：2006.10.1

  A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)ones show low micromolar IC50 values versus E. coli MurB and submicromolar minimal inhibitory concentrations ( MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site.