1-(2-methoxyphenyl)-1H-imidazole-2-carbaldehyde | 51581-64-7

• 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-(2-methoxyphenyl)-1H-imidazole-2-carbaldehyde
• 英文别名: 1-o-Methoxyphenyl-imidazol-2-carboxaldehyd；1-(2-Methoxyphenyl)imidazole-2-carbaldehyde；1-(2-methoxyphenyl)imidazole-2-carbaldehyde
• CAS: 51581-64-7
• 化学式: C₁₁H₁₀N₂O₂
• 分子量: 202.213
• InChiKey: FHDUABNEWFNFQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  四乙基(2-氧代-1,3-丙烷二基)二(膦酸酯) 、 1-(2-methoxyphenyl)-1H-imidazole-2-carbaldehyde 在 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 以30%的产率得到(1E,4E)-1,5-bis(1-(2-methoxyphenyl)-1H-imidazol-2-yl)penta-1,4-dien-3-one
  参考文献：
  名称：

  Optimization of diarylpentadienones as chemotherapeutics for prostate cancer

  摘要：

  Our earlier studies indicate that (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones and (1E,4E)-1,5-bis(1-alkyl-1H-benzo Mimidazol-2-yepenta-1,4-diene-3-ones exhibit up to 121-fold greater antiproliferative potency than curcumin in human prostate cancer cell models, but only 2-10 fold increase in mouse plasma concentrations. The present study aims to further optimize them as anti-prostate cancer agents with both good potency and bioavailability. (1E,4E)-1,5-Bis(1H-imidazol-2-yepenta-1,4-diene-3-one, the potential metabolic product of (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones, was synthesized and evaluated for its anti-proliferative activity. The promising potency of 1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones was completely abolished by removing the 1-alkyl group, suggesting the critical role of an appropriate group on the N1 position. We then envisioned that N-aryl substitution to exclude the C-H bond on the carbon adjacent to the N1 position (a-H) may increase the metabolic stability. Consequently, seven (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yepenta-1,4-dien-3-ones and three (1E,4E)-1,5-bis(1-aryl-1H-benzo [d] imidazol-2-yOpenta-1,4-dien-3-ones, as well as three (1E,4E)-1,5-bis(1-aryl-1H-pyrrolo[3,2-b]pyridine-2-yepenta-1,4-dien-3-ones, were synthesized through a three-step transformation, including N-arylation via Ullmann condensation, formylation, and Horner-Wadsworth-Emmons reaction. Six optimal (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yOpenta-1,4-dien-3-ones exhibit 24- to 375-fold improved potency as compared with curcumin. Replacement of the imidazole with bulkier benzoimidazole and 4-azaindole results in a substantial decrease in the potency. (1E,4E)-1,5-Bis(1-(2-methoxyphenyl)-1H-imidazol-2-yOpenta-1,4-dien-3-one (17d) was established as an optimal compound with both superior potency and good bioavailability that is sufficient to provide the therapeutic efficacy necessary to suppress in vivo tumor growth.

  DOI：

  10.1016/j.bmc.2018.08.018
• 作为产物：
  描述：

  2-溴苯甲醚 在 copper(l) iodide 、 正丁基锂 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 1-(2-methoxyphenyl)-1H-imidazole-2-carbaldehyde
  参考文献：
  名称：

  Optimization of diarylpentadienones as chemotherapeutics for prostate cancer

  摘要：

  Our earlier studies indicate that (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones and (1E,4E)-1,5-bis(1-alkyl-1H-benzo Mimidazol-2-yepenta-1,4-diene-3-ones exhibit up to 121-fold greater antiproliferative potency than curcumin in human prostate cancer cell models, but only 2-10 fold increase in mouse plasma concentrations. The present study aims to further optimize them as anti-prostate cancer agents with both good potency and bioavailability. (1E,4E)-1,5-Bis(1H-imidazol-2-yepenta-1,4-diene-3-one, the potential metabolic product of (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones, was synthesized and evaluated for its anti-proliferative activity. The promising potency of 1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones was completely abolished by removing the 1-alkyl group, suggesting the critical role of an appropriate group on the N1 position. We then envisioned that N-aryl substitution to exclude the C-H bond on the carbon adjacent to the N1 position (a-H) may increase the metabolic stability. Consequently, seven (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yepenta-1,4-dien-3-ones and three (1E,4E)-1,5-bis(1-aryl-1H-benzo [d] imidazol-2-yOpenta-1,4-dien-3-ones, as well as three (1E,4E)-1,5-bis(1-aryl-1H-pyrrolo[3,2-b]pyridine-2-yepenta-1,4-dien-3-ones, were synthesized through a three-step transformation, including N-arylation via Ullmann condensation, formylation, and Horner-Wadsworth-Emmons reaction. Six optimal (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yOpenta-1,4-dien-3-ones exhibit 24- to 375-fold improved potency as compared with curcumin. Replacement of the imidazole with bulkier benzoimidazole and 4-azaindole results in a substantial decrease in the potency. (1E,4E)-1,5-Bis(1-(2-methoxyphenyl)-1H-imidazol-2-yOpenta-1,4-dien-3-one (17d) was established as an optimal compound with both superior potency and good bioavailability that is sufficient to provide the therapeutic efficacy necessary to suppress in vivo tumor growth.

  DOI：

  10.1016/j.bmc.2018.08.018

文献信息

• Optimization of diarylpentadienones as chemotherapeutics for prostate cancer
  作者：Manee Patanapongpibul、Changde Zhang、Guanglin Chen、Shanchun Guo、Qiang Zhang、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.bmc.2018.08.018

  日期：2018.9

  Our earlier studies indicate that (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones and (1E,4E)-1,5-bis(1-alkyl-1H-benzo Mimidazol-2-yepenta-1,4-diene-3-ones exhibit up to 121-fold greater antiproliferative potency than curcumin in human prostate cancer cell models, but only 2-10 fold increase in mouse plasma concentrations. The present study aims to further optimize them as anti-prostate cancer agents with both good potency and bioavailability. (1E,4E)-1,5-Bis(1H-imidazol-2-yepenta-1,4-diene-3-one, the potential metabolic product of (1E,4E)-1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones, was synthesized and evaluated for its anti-proliferative activity. The promising potency of 1,5-bis(1-alkyl-1H-imidazol-2-yepenta-1,4-diene-3-ones was completely abolished by removing the 1-alkyl group, suggesting the critical role of an appropriate group on the N1 position. We then envisioned that N-aryl substitution to exclude the C-H bond on the carbon adjacent to the N1 position (a-H) may increase the metabolic stability. Consequently, seven (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yepenta-1,4-dien-3-ones and three (1E,4E)-1,5-bis(1-aryl-1H-benzo [d] imidazol-2-yOpenta-1,4-dien-3-ones, as well as three (1E,4E)-1,5-bis(1-aryl-1H-pyrrolo[3,2-b]pyridine-2-yepenta-1,4-dien-3-ones, were synthesized through a three-step transformation, including N-arylation via Ullmann condensation, formylation, and Horner-Wadsworth-Emmons reaction. Six optimal (1E,4E)-1,5-bis(1-aryl-1H-imidazol-2-yOpenta-1,4-dien-3-ones exhibit 24- to 375-fold improved potency as compared with curcumin. Replacement of the imidazole with bulkier benzoimidazole and 4-azaindole results in a substantial decrease in the potency. (1E,4E)-1,5-Bis(1-(2-methoxyphenyl)-1H-imidazol-2-yOpenta-1,4-dien-3-one (17d) was established as an optimal compound with both superior potency and good bioavailability that is sufficient to provide the therapeutic efficacy necessary to suppress in vivo tumor growth.