1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)-1H-imidazole | 1253697-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)-1H-imidazole
• 英文别名: 1-(benzenesulfonyl)-2-(3,4,5-trimethoxyphenyl)imidazole
• CAS: 1253697-53-8
• 化学式: C₁₈H₁₈N₂O₅S
• 分子量: 374.417
• InChiKey: WMMGMHJCOWBLMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  88
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)-1H-imidazole 、 对氟苯甲酰氯 在 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 0.17h， 以18.8%的产率得到(4-fluorophenyl)(1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-yl)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醛 在 ammonium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 mineral oil 为溶剂， 反应 27.0h， 生成 1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)-1H-imidazole
  参考文献：
  名称：

  设计，合成和生物学评估以微管蛋白聚合为潜在抗癌剂的1-取代-2-芳基咪唑。

  摘要：

  基于我们先前报道的ABI（2-芳基-4-苄基咪唑）类似物和康布雷他汀A-4（CA-4）的结构，设计和合成了一系列新型的1-取代-2-芳基咪唑（SAI）。 。这些化合物对六种人类癌细胞系表现出有效的抗增殖活性，IC50值在纳摩尔范围内。其中，化合物3X表现出最佳的抗癌活性，平均IC50值为〜100 nM。该化合物通过抑制微管蛋白聚合来维持作用机理，从而导致细胞停滞在G2 / M期并凋亡。体内功效研究表明，3X在MDA-MB-468裸鼠异种移植模型中以60 mg / kg的TGI（肿瘤生长抑制）为77％抑制肿瘤生长非常有效，而不会引起明显的毒性。此外，3X显示出比CA-4（2.83μg/ mL）更好的水溶性（36.70μg/ mL）。分子模型研究表明3X与微管蛋白中的秋水仙碱结合位点结合良好。我们的结果表明，新型SAI类似物作为潜在的抗癌药物值得进一步研究。

  DOI：

  10.1016/j.ejmech.2019.111732

文献信息

• COMPOUNDS FOR TREATMENT OF CANCER
  申请人：Gtx, Inc.

  公开号：EP2608671B1

  公开（公告）日：2018-12-12
• Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents
  作者：Ling Li、Dongling Quan、Jingxuan Chen、Jiahao Ding、Jinwu Zhao、Lin Lv、Jianjun Chen

  DOI：10.1016/j.ejmech.2019.111732

  日期：2019.12

  A series of novel 1-substituted-2-aryl imidazoles (SAI) were designed and synthesized based on our previously reported ABI (2-Aryl-4-Benzoyl Imidazole) analogs and on the structure of combretastatin A-4 (CA-4). These compounds showed potent antiproliferative activities against six human cancer cell lines with IC50 values in nano molar range. Among them, compound 3X exhibited the best anticancer activity

  基于我们先前报道的ABI（2-芳基-4-苄基咪唑）类似物和康布雷他汀A-4（CA-4）的结构，设计和合成了一系列新型的1-取代-2-芳基咪唑（SAI）。 。这些化合物对六种人类癌细胞系表现出有效的抗增殖活性，IC50值在纳摩尔范围内。其中，化合物3X表现出最佳的抗癌活性，平均IC50值为〜100 nM。该化合物通过抑制微管蛋白聚合来维持作用机理，从而导致细胞停滞在G2 / M期并凋亡。体内功效研究表明，3X在MDA-MB-468裸鼠异种移植模型中以60 mg / kg的TGI（肿瘤生长抑制）为77％抑制肿瘤生长非常有效，而不会引起明显的毒性。此外，3X显示出比CA-4（2.83μg/ mL）更好的水溶性（36.70μg/ mL）。分子模型研究表明3X与微管蛋白中的秋水仙碱结合位点结合良好。我们的结果表明，新型SAI类似物作为潜在的抗癌药物值得进一步研究。
• 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.