2-hexamethylenetetramino-1-(3,4-dimethoxyphenyl)ethanone-2-ium bromide | 1234216-77-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-hexamethylenetetramino-1-(3,4-dimethoxyphenyl)ethanone-2-ium bromide
• 英文别名: 1-(3,4-Dimethoxyphenyl)-2-(3,5,7-triaza-1-azoniatricyclo[3.3.1.13,7]decan-1-yl)ethanone;bromide
• CAS: 1234216-77-3
• 化学式: Br*C₁₆H₂₃N₄O₃
• 分子量: 399.288
• InChiKey: BAEPZKKZDBZJLR-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  45.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-hexamethylenetetramino-1-(3,4-dimethoxyphenyl)ethanone-2-ium bromide 在 氢溴酸 作用下， 以 甲醇 为溶剂， 以95%的产率得到2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid
  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：

  邻苯二甲醚 在 N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酸 、 zinc(II) chloride 作用下， 以 氯仿 、 乙腈 为溶剂， 生成 2-hexamethylenetetramino-1-(3,4-dimethoxyphenyl)ethanone-2-ium bromide
  参考文献：
  名称：

  合成5-芳基和5-碘吡咯并[2,3- d ]嘧啶的简便方法

  摘要：

  已经开发出一种有效且环境友好的一锅法，用于合成4-氨基-5-芳基吡咯并[2,3- d ]嘧啶。邻苯二甲酰亚胺苯乙酮与氰基乙酰胺，得到2-氨基-4-苯基-1- ħ吡咯-3-甲酰胺，其进一步转化为5-芳基-3- ħ吡咯并[2,3- d ]嘧啶-4-酮。还开发了用于合成4-氨基-5-碘吡咯并[2，3- d ]嘧啶的新方法。

  DOI：

  10.1002/jhet.1937

文献信息

• Facile Methods for the Synthesis of 5-Aryl and 5-Iodo Pyrrolo[2,3-<i>d</i>]pyrimidines
  作者：K. Venkata Rao、M. Raghu Prasad、A. Raghuram Rao

  DOI：10.1002/jhet.1937

  日期：2014.8

  environmentally benign one-pot method has been developed for the synthesis of 4-amino-5-arylpyrrolo[2,3-d]pyrimidines. Phthalimido acetophenones were reacted with cyanoacetamide to give 2-amino-4-phenyl-1H-pyrrole-3-carboxamides, which were further converted to 5-aryl-3H-pyrrolo[2,3-d]pyrimidin-4-ones. A novel method is also developed for the synthesis of 4-amino-5-iodopyrrolo[2,3-d]pyrimidines.

  已经开发出一种有效且环境友好的一锅法，用于合成4-氨基-5-芳基吡咯并[2,3- d ]嘧啶。邻苯二甲酰亚胺苯乙酮与氰基乙酰胺，得到2-氨基-4-苯基-1- ħ吡咯-3-甲酰胺，其进一步转化为5-芳基-3- ħ吡咯并[2,3- d ]嘧啶-4-酮。还开发了用于合成4-氨基-5-碘吡咯并[2，3- d ]嘧啶的新方法。
• 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.