[2-(4-Methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazol-4-yl](3,4,5-trimethoxyphenyl)methanone | 1253697-45-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-Methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazol-4-yl](3,4,5-trimethoxyphenyl)methanone
• 英文别名: [1-(benzenesulfonyl)-2-(4-methoxyphenyl)imidazol-4-yl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1253697-45-8
• 化学式: C₂₆H₂₄N₂O₇S
• 分子量: 508.552
• InChiKey: XETPIZSBMLCHBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-(4-Methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazol-4-yl](3,4,5-trimethoxyphenyl)methanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以10.2%的产率得到(2-(4-methoxyphenyl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of Novel 2-Aryl-4-benzoyl-imidazoles Targeting the Colchicines Binding Site in Tubulin As Potential Anticancer Agents

  摘要：

  A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC50 of the most active compound (5da) was 15.7 nM. ABI analogues have substantially improved aqueous solubility (48.9 mu g/mL for 5ga vs 0.909 mu g/mL for SMART-I, 0.137 mu g/mL for paclitaxel, and 1.04 mu g/mL for combretastatin A4). Mechanism of action studies indicate that the anticancer activity of ABI analogues is through inhibition of tubulin polymerization by interacting with the colchicine binding site. Unlike paclitaxel and colchicine, the ABI compounds were equally potent against multidrug resistant cancer cells and the sensitive parental melanoma cancer cells. In vivo results indicated that 5cb was more effective than DTIC in inhibiting melanoma xenograph tumor growth. Our results suggest that the novel ABI compounds may be developed to effectively treat drug-resistant tumors.

  DOI：

  10.1021/jm100884b
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酰氯 、 2-(4-methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazole 在 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 0.17h， 生成 [2-(4-Methoxyphenyl)-1-(phenylsulfonyl)-1H-imidazol-4-yl](3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of Novel 2-Aryl-4-benzoyl-imidazoles Targeting the Colchicines Binding Site in Tubulin As Potential Anticancer Agents

  摘要：

  A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC50 of the most active compound (5da) was 15.7 nM. ABI analogues have substantially improved aqueous solubility (48.9 mu g/mL for 5ga vs 0.909 mu g/mL for SMART-I, 0.137 mu g/mL for paclitaxel, and 1.04 mu g/mL for combretastatin A4). Mechanism of action studies indicate that the anticancer activity of ABI analogues is through inhibition of tubulin polymerization by interacting with the colchicine binding site. Unlike paclitaxel and colchicine, the ABI compounds were equally potent against multidrug resistant cancer cells and the sensitive parental melanoma cancer cells. In vivo results indicated that 5cb was more effective than DTIC in inhibiting melanoma xenograph tumor growth. Our results suggest that the novel ABI compounds may be developed to effectively treat drug-resistant tumors.

  DOI：

  10.1021/jm100884b

文献信息

• Discovery of Novel 2-Aryl-4-benzoyl-imidazoles Targeting the Colchicines Binding Site in Tubulin As Potential Anticancer Agents
  作者：Jianjun Chen、Zhao Wang、Chien-Ming Li、Yan Lu、Pavan K. Vaddady、Bernd Meibohm、James T. Dalton、Duane D. Miller、Wei Li

  DOI：10.1021/jm100884b

  日期：2010.10.28

  A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC50 of the most active compound (5da) was 15.7 nM. ABI analogues have substantially improved aqueous solubility (48.9 mu g/mL for 5ga vs 0.909 mu g/mL for SMART-I, 0.137 mu g/mL for paclitaxel, and 1.04 mu g/mL for combretastatin A4). Mechanism of action studies indicate that the anticancer activity of ABI analogues is through inhibition of tubulin polymerization by interacting with the colchicine binding site. Unlike paclitaxel and colchicine, the ABI compounds were equally potent against multidrug resistant cancer cells and the sensitive parental melanoma cancer cells. In vivo results indicated that 5cb was more effective than DTIC in inhibiting melanoma xenograph tumor growth. Our results suggest that the novel ABI compounds may be developed to effectively treat drug-resistant tumors.