1-(3-chlorophenyl)-1H-benzo[d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(3-chlorophenyl)-1H-benzo[d]imidazole
• 英文别名: 1-(3-chlorophenyl)benzimidazole；1-(3-chlorophenyl)-1H-benzimidazole；1-(3-Chlor-phenyl)-1H-benzimidazol
• 化学式: C₁₃H₉ClN₂
• 分子量: 228.681
• InChiKey: PPYWUMHDJBIKTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-chlorophenyl)-1H-benzo[d]imidazole 在 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 4.0h， 生成 (1E,4E)-1,5-bis(1-(3-chlorophenyl)-1H-benzo[d]imidazole-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：

  苯并咪唑 、 间氯溴苯 在 copper(l) iodide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以25%的产率得到1-(3-chlorophenyl)-1H-benzo[d]imidazole
  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

• <i>N</i>,<i>O</i>-Bidentate ligand-tunable copper(<scp>ii</scp>) complexes as a catalyst for Chan–Lam coupling reactions of arylboronic acids with 1<i>H</i>-imidazole derivatives
  作者：Xuefeng Jia、Pai Peng

  DOI：10.1039/c8ob02254b

  日期：——

  An efficient procedure for Chan–Lam coupling reactions of arylboronic acids with 1H-imidazole derivatives using N,O-bidentate ligand-tunable copper(II) complexes as a catalyst under base-free conditions has been developed. This protocol features mild reaction conditions, high yields and compatibility with different functional groups, providing a direct and facile strategy for the construction of C–N

  已经开发了一种有效的程序，用于在无碱条件下使用N，O-双齿配体可调铜（II）配合物作为催化剂，使芳基硼酸与1 H-咪唑衍生物进行Chan-Lam偶联反应。该方案具有温和的反应条件，高收率和与不同官能团的相容性，为构建C–N键和合成杂环化合物提供了直接而简便的策略。
• Catalyst-Free N-Arylation Using Unactivated Fluorobenzenes
  作者：Frederik Diness、David P. Fairlie

  DOI：10.1002/anie.201202149

  日期：2012.8.6

  Caught in a ‘SNAr'e: A one‐step, high‐yielding, catalyst‐free method is described for N‐arylation of azoles and indoles from unactivated monofluorobenzenes. This SNAr reaction tolerates a wide range of substituents and can also generate halogenated N‐aryl products. The reaction can also be performed simultaneously with or subsequent to a copper‐ or palladium‐catalyzed cross‐coupling reaction in the

  夹在A的Ñ Ar'e：一步法，高产，不含催化剂的方法，是从非活化monofluorobenzenes唑类和吲哚类的N-芳基化所述。该S Ñ氩反应容许宽范围的取代基，并且还可以生成卤代N-芳基产物。该反应也可以用同时执行或以一个铜或在相同的罐的钯-催化的交叉偶联反应之后进行。
• KOH/Adogen 464/Proline System for Highly Effective Cu-Catalyzed “On-Water” N–H Arylation of Heteroaromatic Compounds
  作者：E. Abele、R. Abele

  DOI：10.1007/s10593-013-1389-8

  日期：2013.12
• ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES
  申请人：UNIVERSAL DISPLAY CORPORATION

  公开号：US20240190901A1

  公开（公告）日：2024-06-13

  Provided are compounds comprising as a central moiety a 6-membered aromatic ring which is fused to a 5-membered heterocyclic ring comprising at least two nitrogen atoms. Also provided are formulations comprising these compounds. Further provided are organic light emitting devices (OLEDs) as well as related consumer products that utilize these compounds.
• 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.