2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid | 1234216-79-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid
• 英文别名: 2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromide；2-Amino-1-(3,4-dimethoxyphenyl)ethan-1-one hydrobromide；2-amino-1-(3,4-dimethoxyphenyl)ethanone;hydrobromide
• CAS: 1234216-79-5
• 化学式: BrH*C₁₀H₁₃NO₃
• mdl: MFCD22378787
• 分子量: 276.13
• InChiKey: HYLGBCRSSGXFMG-UHFFFAOYSA-N

物化性质

• 熔点：
  236-238 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.29
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid 在 potassium tert-butylate 、 sodium hydride 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 0.5h， 生成 3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione
  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
• 作为产物：
  描述：

  溴代-3,4-二甲氧基苯乙酮 在 氢溴酸 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 2.0h， 生成 2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid
  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

• [EN] COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：PROTEOTECH INC

  公开号：WO2012118935A1

  公开（公告）日：2012-09-07

  Compounds and their pharmaceutically acceptable salts for treatment of synucleinopathies, such as Parkinson's disease and tauopathies.

  用于治疗α-突触核复合物病和tau蛋白病的化合物及其药用盐。
• 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.
• Structure–Activity Relationship Study of Permethyl Ningalin B Analogues as P-Glycoprotein Chemosensitizers
  作者：Jin Wen Bin、Iris L. K. Wong、Xuesen Hu、Zhang Xiao Yu、Li Fu Xing、Tao Jiang、Larry M. C. Chow、Wan Sheng Biao

  DOI：10.1021/jm400930e

  日期：2013.11.27

  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.