1-benzyl-3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione | 1234216-70-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-benzyl-3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione
• 英文别名: 1-benzyl-3,4-bis(3,4-dimethoxyphenyl)pyrrole-2,5-dione
• CAS: 1234216-70-6
• 化学式: C₂₇H₂₅NO₆
• 分子量: 459.499
• InChiKey: MWUVYPHPTQFHDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-benzyl-3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione 在 劳森试剂 作用下， 以 甲苯 为溶剂， 以68%的产率得到1-benzyl-3,4-bis(3,4-dimethoxyphenyl)-5-thioxo-1H-pyrrol-2(5H)-one
  参考文献：
  名称：

  Design and Syntheses of Permethyl Ningalin B Analogues: Potent Multidrug Resistance (MDR) Reversal Agents of Cancer Cells

  摘要：

  A series of novel N-arylalkyl-3,4-diaryl-substituted pyrrole-2,5-diones were synthesized. They exhibited promising P-gp modulating activity in a P-gp overexpressing breast cancer cell line (LCC6MDR). Compound 6 (with three methoxy groups at D-ring) displayed the highest P-gp modulating activity. 6 at 1 mu M can sensitize LCC6MDR cells toward paclitaxel by 18.2-fold. Interestingly, a synergy on modulating P-gp was noted when 6 and 25 were used together (fractional inhibitory concentration index FICI = 0.42). Combination of 6 (0.5 mu M) and 25 (0.5 mu M) resulted in a 66-fold sensitization of LCC6MDR cells toward paclitaxel. They also reversed P-gp mediated doxorubicin (DOX) and vincristine resistance. Kinetic characterization suggests that permethyl ningalin B analogues likely act as a noncompetitive inhibitor of P-gp-mediated DOX transport (K-i = 5.4-5.8 mu M). The present study demonstrates that synthetic analogues of permethyl ningalin B can be employed as effective and safe modulators of P-gp-mediated drug resistance in cancer cells.

  DOI：

  10.1021/jm100035c
• 作为产物：
  描述：

  溴甲苯 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium phosphate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 反应 3.67h， 生成 1-benzyl-3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Discovery of new effective N-alkyl-3,4-diarylmaleimides-based drugs for reversing the bacterial resistance to rhodamine 6G in Bacillus subtilis

  摘要：

  多药耐药性（MDR）是全世界都非常关注的问题。目前亟需开发出能攻击表现出 MDR 表型的靶细胞的新药。本研究的目的是评估新型 N-烷基-3,4-二芳基马来酰亚胺对对罗丹明 6G 产生耐药性的枯草芽孢杆菌的逆转作用，以此作为其作为外排泵调节剂的活性指标以及作为新型抗菌药物的其他潜力。采用最小抑菌浓度（MIC）法测试了 N-烷基-3-4-二芳基马来酰亚胺对枯草杆菌野生型、对罗丹明 6G 耐药的枯草杆菌以及从临床样本中分离的 MDR 细菌（大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌、粪肠球菌和鲍曼不动杆菌）的外排泵调节作用。此外，还对它们在临床分离物上的抗菌活性进行了评估。五种 N-烷基-3,4-二芳基马来酰亚胺对芽孢杆菌模型以及从临床样本中分离出来的细菌的耐药性具有最高的逆转活性。N-烷基-3,4-二芳基马来酰亚胺对从临床样本中分离出来的细菌具有抗菌活性。结果表明，N-烷基-3,4-二芳基马来酰亚胺在逆转 MDR 表型和作为抗菌剂方面具有潜在的活性，可被视为改善对耐药细胞化疗的潜在分子。

  DOI：

  10.1007/s11696-019-00992-7

文献信息

• Design and Syntheses of Permethyl Ningalin B Analogues: Potent Multidrug Resistance (MDR) Reversal Agents of Cancer Cells
  作者：Pu Yong Zhang、Iris L. K. Wong、Clare S. W. Yan、Xiao Yu Zhang、Tao Jiang、Larry M. C. Chow、Sheng Biao Wan

  DOI：10.1021/jm100035c

  日期：2010.7.22

  A series of novel N-arylalkyl-3,4-diaryl-substituted pyrrole-2,5-diones were synthesized. They exhibited promising P-gp modulating activity in a P-gp overexpressing breast cancer cell line (LCC6MDR). Compound 6 (with three methoxy groups at D-ring) displayed the highest P-gp modulating activity. 6 at 1 mu M can sensitize LCC6MDR cells toward paclitaxel by 18.2-fold. Interestingly, a synergy on modulating P-gp was noted when 6 and 25 were used together (fractional inhibitory concentration index FICI = 0.42). Combination of 6 (0.5 mu M) and 25 (0.5 mu M) resulted in a 66-fold sensitization of LCC6MDR cells toward paclitaxel. They also reversed P-gp mediated doxorubicin (DOX) and vincristine resistance. Kinetic characterization suggests that permethyl ningalin B analogues likely act as a noncompetitive inhibitor of P-gp-mediated DOX transport (K-i = 5.4-5.8 mu M). The present study demonstrates that synthetic analogues of permethyl ningalin B can be employed as effective and safe modulators of P-gp-mediated drug resistance in cancer cells.
• Discovery of new effective N-alkyl-3,4-diarylmaleimides-based drugs for reversing the bacterial resistance to rhodamine 6G in Bacillus subtilis
  作者：Claudia Leticia Mendoza-Macías、Cesar Rogelio Solorio-Alvarado、Angel Josabad Alonso-Castro、Clara Alba-Betancourt、Martha Alicia Deveze-Álvarez、Felipe Padilla-Vaca、Arturo Reyes-Gualito

  DOI：10.1007/s11696-019-00992-7

  日期：2020.5

  Multidrug resistance (MDR) is a great concern worldwide. There is a great need to develop new drugs with the potential to attack target cells that show MDR phenotype. The purpose of this study was to assess the reversing effect of new N-alkyl-3,4-diarylmaleimides on Bacillus subtilis resistant to rhodamine 6G as an indicator of its activity as modulators of efflux pumps and their additional potential as new antimicrobials. The efflux pump modulator effects of N-alkyl-3-4-diarylmaleimides were tested using the minimal inhibitory concentration (MIC) method on B. subtilis wild type and B. subtilis resistant to R6G, as well as on MDR bacteria isolated from clinical samples (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecium, and Acinetobacter baumannii). In addition, their antimicrobial activity was evaluated on clinical isolates. Five N-alkyl-3,4-diarylmaleimides showed the highest reversing activity on the resistance in the Bacillus model as well as with the bacteria isolated from clinical samples. Antimicrobial activity was observed in N-alkyl-3,4-diarylmaleimides against bacteria isolated from clinical samples. The results suggest that N-alkyl-3,4-diarylmaleimides have a potential activity in reversing MDR phenotype and as antimicrobials and may be considered as a potentially molecules to improve chemotherapy on resistant cells.

  多药耐药性（MDR）是全世界都非常关注的问题。目前亟需开发出能攻击表现出 MDR 表型的靶细胞的新药。本研究的目的是评估新型 N-烷基-3,4-二芳基马来酰亚胺对对罗丹明 6G 产生耐药性的枯草芽孢杆菌的逆转作用，以此作为其作为外排泵调节剂的活性指标以及作为新型抗菌药物的其他潜力。采用最小抑菌浓度（MIC）法测试了 N-烷基-3-4-二芳基马来酰亚胺对枯草杆菌野生型、对罗丹明 6G 耐药的枯草杆菌以及从临床样本中分离的 MDR 细菌（大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌、粪肠球菌和鲍曼不动杆菌）的外排泵调节作用。此外，还对它们在临床分离物上的抗菌活性进行了评估。五种 N-烷基-3,4-二芳基马来酰亚胺对芽孢杆菌模型以及从临床样本中分离出来的细菌的耐药性具有最高的逆转活性。N-烷基-3,4-二芳基马来酰亚胺对从临床样本中分离出来的细菌具有抗菌活性。结果表明，N-烷基-3,4-二芳基马来酰亚胺在逆转 MDR 表型和作为抗菌剂方面具有潜在的活性，可被视为改善对耐药细胞化疗的潜在分子。