3,4-bis(3',4'-dimethoxyphenyl)-1H-pyrrol-2(5H)-one | 1234216-81-9

• 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: 3,4-bis(3',4'-dimethoxyphenyl)-1H-pyrrol-2(5H)-one
• 英文别名: 3,4-Bis(3,4-dimethoxyphenyl)-1,2-dihydropyrrol-5-one
• CAS: 1234216-81-9
• 化学式: C₂₀H₂₁NO₅
• 分子量: 355.39
• InChiKey: KHYBRVBOHNOXJY-UHFFFAOYSA-N

物化性质

• 熔点：
  170-172 °C
• 沸点：
  570.3±50.0 °C(predicted)
• 密度：
  1.205±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-bis(3',4'-dimethoxyphenyl)-1H-pyrrol-2(5H)-one 在 三氟化硼乙醚 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以96%的产率得到2,3-dihydro-5,6,9,10-tetramethoxy-1H-dibenzo[e,g]-isoindole-1-one
  参考文献：
  名称：

  通过 Scholl 型氧化环化反应制备二苯并[e,g]异吲哚-1-酮

  摘要：

  开发了二苯并[ e , g ]异吲哚-1-酮的灵活合成方法。二苯并[ e , g ]异吲哚-1-酮代表生物吲哚并[2,3- a ]吡咯并[3,4- c ]咔唑-5-酮（吲哚并咔唑）的简化苯类似物，这些化合物已被证明具有广泛的用途生物活性。标题化合物的合成涉及特特拉姆酸磺酸盐。通过 Suzuki-Miyaura 交叉偶联反应在杂环的 C4 处引入不同的芳基。最后，由苯碘(III)双(三氟乙酸酯)(PIFA)介导的温和Scholl型氧化环化将后面的一些化合物转化为相应的二苯并[ e , g ]异吲哚-1-酮。对氧化环化的系统研究揭示了以下反应活性趋势：3,4-二甲氧基苯基≫3-甲氧基苯基>3,4,5-三甲氧基苯基>4-甲氧基苯基≈苯基。总体而言，氧化环化需要至少两个甲氧基分布在芳环中，其中至少一个必须位于环化位点的对位。

  DOI：

  10.1021/jo501185f
• 作为产物：
  描述：

  (3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide) 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 2.0h， 以50%的产率得到3,4-bis(3',4'-dimethoxyphenyl)-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

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.
• Preparation of Dibenzo[<i>e</i>,<i>g</i>]isoindol-1-ones via Scholl-Type Oxidative Cyclization Reactions
  作者：Amy A. van Loon、Maeve K. Holton、Catherine R. Downey、Taryn M. White、Carly E. Rolph、Stephen R. Bruening、Guanqun Li、Katherine M. Delaney、Sarah J. Pelkey、Erin T. Pelkey

  DOI：10.1021/jo501185f

  日期：2014.9.5

  at C4 of the heterocyclic ring via Suzuki–Miyaura cross-coupling reactions. Finally, mild Scholl-type oxidative cyclizations mediated by phenyliodine(III) bis(trifluoroacetate) (PIFA) converted some of the latter compounds into the corresponding dibenzo[e,g]isoindol-1-ones. A systematic study of the oxidative cyclization revealed the following reactivity trend: 3,4-dimethoxyphenyl ≫ 3-methoxyphenyl >

  开发了二苯并[ e , g ]异吲哚-1-酮的灵活合成方法。二苯并[ e , g ]异吲哚-1-酮代表生物吲哚并[2,3- a ]吡咯并[3,4- c ]咔唑-5-酮（吲哚并咔唑）的简化苯类似物，这些化合物已被证明具有广泛的用途生物活性。标题化合物的合成涉及特特拉姆酸磺酸盐。通过 Suzuki-Miyaura 交叉偶联反应在杂环的 C4 处引入不同的芳基。最后，由苯碘(III)双(三氟乙酸酯)(PIFA)介导的温和Scholl型氧化环化将后面的一些化合物转化为相应的二苯并[ e , g ]异吲哚-1-酮。对氧化环化的系统研究揭示了以下反应活性趋势：3,4-二甲氧基苯基≫3-甲氧基苯基>3,4,5-三甲氧基苯基>4-甲氧基苯基≈苯基。总体而言，氧化环化需要至少两个甲氧基分布在芳环中，其中至少一个必须位于环化位点的对位。