(3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide) | 861597-70-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide)
• 英文别名: C-(3,4-Dimethoxy-phenyl)-N-(3,4-dimethoxy-phenacyl)-acetamid；(3,4-Dimethoxy-phenyl)-essigsaeure-(3,4-dimethoxy-phenacylamid)；2-[C-(3,4-Dimethoxy-phenyl)-acetamino]-1-(3,4-dimethoxy-phenyl)-aethanon-(1)；ω-(3.4-Dimethoxy-phenacetamino)-3.4-dimethoxy-acetophenon；4-Homoveratroylaminoacetyl-brenzcatechin-dimethylaether；ω-Homoveratroylamino-acetoveratron；2-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]acetamide
• CAS: 861597-70-8
• 化学式: C₂₀H₂₃NO₆
• 分子量: 373.406
• InChiKey: UDTZZNUPGCLAFJ-UHFFFAOYSA-N

物化性质

• 熔点：
  142 °C
• 沸点：
  600.6±55.0 °C(predicted)
• 密度：
  1.179±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide) 在 磷酸酐 、 sodium amalgam 、 乙醇 、 溶剂黄146 、 xylene 作用下， 生成 罂粟碱
  参考文献：
  名称：

  Pictet; Gams, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1909, vol. 149, p. 212

  摘要：

  DOI：
• 作为产物：
  描述：

  溴代-3,4-二甲氧基苯乙酮 在 氢溴酸 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 2.5h， 生成 (3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide)
  参考文献：
  名称：

  Structure–Activity Relationship Study of Permethyl Ningalin B Analogues as P-Glycoprotein Chemosensitizers

  摘要：

  A novel series of permethyl ningalin B analogues were synthesized and evaluated for their P-glycoprotein (P-gp)-modulating activities in a P-gp-overexpressing breast cancer cell line (LCC6MDR). Compounds 35 and 37, which possess one methoxy group and one benzyloxy group at aryl ring C, displayed the most potent Pgp-modulating activity. A 1 pM concentration of 35 and 37 resensitized LCC6MDR cells toward paclitaxel by 42.7-fold, with respective EC50 values of 93.5 and 110.0 nM. Their mechanism of P-gp modulation is associated with an increase in intracellular drug accumulation. Their advantages also include low cytotoxicity (IC50 for L929 fibroblast >100 mu M) and high therapeutic indexes (>909 after normalization with their EC50 values). 35 is not a substrate of P-gp. They are potentially dual-selective modulators for both P-gp and breast cancer resistance protein transporters. The present study demonstrates that these new compounds can be employed as effective and safe modulators of Pgp-mediated drug resistance in cancer cells.

  DOI：

  10.1021/jm400930e

文献信息

• Extending the structure−activity relationship study of marine natural ningalin B analogues as P-glycoprotein inhibitors
  作者：Chao Yang、Iris L.K. Wong、Kai Peng、Zhen Liu、Peng Wang、Tingfu Jiang、Tao Jiang、Larry M.C. Chow、Sheng Biao Wan

  DOI：10.1016/j.ejmech.2016.09.070

  日期：2017.1

  In the present study, a total of 25 novel ningalin B analogues were synthesized and evaluated for their P-gp modulating activity in a P-gp overexpressed breast cancer cell line LCC6MDR. Preliminary structure-activity study shows that A ring and its two methoxy groups are important pharmacophores for P-gp inhibiting activity. Among all derivatives, 23 is the most potent P-gp modulator with EC50 of 120–165 nM

  在本研究中，总共合成了25种新的宁格灵B类似物，并评估了它们在过表达P-gp的乳腺癌细胞LCC6MDR中的P-gp调节活性。初步的结构活性研究表明，A环及其两个甲氧基是抑制P-gp活性的重要药效团。在所有衍生物中，23是最有效的P-gp调节剂，在逆转紫杉醇，DOX，长春碱和长春新碱的抗性方面，EC 50为120-165 nM。与维拉帕米相比，选择指数至少大于606相对安全。机理研究表明，化合物23通过抑制P-gp的转运活性来逆转P-gp介导的耐药性，从而恢复细胞内药物的积累。总而言之，我们的研究表明，宁格灵B类似物23是一种无细胞毒性且有效的P-gp化学增敏剂，可在将来用于逆转P-gp介导的临床癌症药物耐药性。
• 76. Attempts to prepare derivatives of 1 : 2-dihydroisoquinoline. New interpretation of J. S. Buck's experiments on the synthesis of so-called 1 : 2-dihydropapaverine
  作者：P. C. Young、Robert Robinson

  DOI：10.1039/jr9330000275

  日期：——
• 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.
• 1,2-DIHYDROPAPAVERINE AND MODIFIED SYNTHESES OF PAPAVERINE AND PAPAVERALDINE (XANTHALINE)
  作者：Johannes S. Buck

  DOI：10.1021/ja01372a023

  日期：1930.9