(E)-1-(1H-benzo[d]imidazol-2-yl)-3-phenylprop-2-en-1-one | 670749-91-4

• 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: (E)-1-(1H-benzo[d]imidazol-2-yl)-3-phenylprop-2-en-1-one
• 英文别名: (2E)-1-(1H-benzimidazol-2-yl)-3-phenyl-2-propen-1-one；(2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-one；1-(1H-benzimidazole-2-yl)-3-phenyl-2-propen-1-one；1-(1H-benzimidazol-2-yl)-3-phenyl-2-propen-1-one；1-(benzimidazol-2-yl)-3-phenylprop-2-en-1-one；2-Cinnamoylbenzimidazole；(E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-one
• CAS: 670749-91-4
• 化学式: C₁₆H₁₂N₂O
• 分子量: 248.284
• InChiKey: HRDWTSALKOENCD-ZHACJKMWSA-N

物化性质

• 熔点：
  194-196 °C
• 沸点：
  487.4±38.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-1-(1H-benzo[d]imidazol-2-yl)-3-phenylprop-2-en-1-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-(5-phenyl-4,5-dihydro-1H-3-pyrazolyl)-1H-benzimidazole
  参考文献：
  名称：

  Pyrazoline bearing benzimidazoles: Search for anticancer agent

  摘要：

  2-acetyl benzimidazole was allowed to react with substituted aromatic aldehydes to get desired intermediate chalcones (2a-g), the cyclocondensation of these intermediates with hydrazine hydrate and phenyl hydrazine in two separate reactions yielded pyrazoline derivatives (3a-g & 4a-g respectively). Among the synthesize compounds, six compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the selected compounds, (4f) 2-[5-(3,4-dimethoxyphenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1H-benzimidazole (NSC 748326) was found to be the most active candidate of the series and selected for further evaluation at five dose level screening. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.09.032
• 作为产物：
  描述：

  2-(1-羟乙基)苯并咪唑 在 potassium dichromate 、 硫酸 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 12.33h， 生成 (E)-1-(1H-benzo[d]imidazol-2-yl)-3-phenylprop-2-en-1-one
  参考文献：
  名称：

  Microwave Assisted Synthesis, Physico-chemical Properties and Antioxidant Activity of a,b-Unsaturated Benzimidazole Derivatives Incorporated with Baritone Moiety

  摘要：

  通过传统方法和微波辅助方法合成了一系列 (2E)-1-(H- 苯并咪唑-2-基)-3-取代苯基 2-丙烯-1-酮与巴比妥（5a-g）的连接物。苯并咪唑查耳酮（4a-g）是由 2-乙酰基苯并咪唑（3a）与不同的芳香醛缩合而成。这些查耳酮在乙酸介质中与巴比妥酸反应后，得到了 a、b-不饱和苯并咪唑衍生物。根据红外光谱、1H NMR、质谱和元素分析，确定了所有最终化合物的结构。衍生物的药效和理化性质由 actelion、molsoft、molinspiration 和 ACD ChemDraw Ultra 11.0 软件测定。最终产品具有良好的药物相似性和药物评分。用 DPPH 法对所有最终合成的化合物进行了抗氧化性筛选，如清除自由基。在合成的化合物中，(5f)、(5c)和(5d)表现出良好的抗氧化活性，而所有其他衍生物则表现出中等活性。

  DOI：

  10.14233/ajchem.2013.13187

文献信息

• Design, synthesis, and<i>in vitro</i>biological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors of<i>Mycobacterium tuberculosis</i>
  作者：Goverdhan Surineni、Yamin Gao、Muzammal Hussain、Zhiyong Liu、Zhili Lu、Chiranjibi Chhotaray、Md Mahmudul Islam、H. M. Adnan Hameed、Tianyu Zhang

  DOI：10.1039/c8md00389k

  日期：——

  requiring the development of novel drugs in order to improve treatment outcomes. Here, as an effort to identify novel and effective antitubercular agents, we designed and synthesized a series of novel substituted benzimidazolallylidenehydrazinylmethylthiazole derivatives via a multi-component molecular hybridization approach with single molecular architecture. Our design strategy involved assembling

  近年来，结核病（TB）已成为最重要的公共卫生问题之一。抗生素治疗仍然是结核病控制策略的支柱，但分枝杆菌耐药性的增加敲响了警钟，需要开发新药以改善治疗结果。在这里，为了寻找新型有效的抗结核药物，我们通过单分子结构的多组分分子杂交方法设计并合成了一系列新型取代苯并咪唑烯丙肼基甲基噻唑衍生物。我们的设计策略涉及通过缩合反应组装抗结核药效团片段苯并咪唑、2-氨基噻唑和取代的α,β-不饱和酮。所有新合成的化合物均通过核磁共振和质谱数据进行了全面表征，并评估了针对结核分枝杆菌H37Ra 菌株的体外生物活性。从生物学评价数据中，我们鉴定了一些有效的化合物，其中8g和7e是最活跃的化合物（均具有2.5 μg mL -1的MIC值）。此外，化合物8g表现出较低的细胞毒性。我们认为化合物8g可以作为进一步先导化合物优化研究的化学探针，总体目标是开发新型有效的抗结核药物。
• Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents
  作者：Lin-tao Wu、Zhi Jiang、Jia-jia Shen、Hong Yi、Yue-chen Zhan、Ming-quan Sha、Zhen Wang、Si-tu Xue、Zhuo-rong Li

  DOI：10.1016/j.ejmech.2016.03.029

  日期：2016.5

  derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06–3.64 μM and 0.04–9.80 μM, respectively. Their antiproliferative activities were

  设计并合成了一系列新型的苯并咪唑-2-取代的苯基或吡啶丙基乙烯酮衍生物。然后评估这些衍生物的生物活性作为潜在的抗肿瘤剂。在体外测定了这些化合物对HCT116，MCF-7和HepG2细胞系的生长抑制活性。化合物A 1和A 7对癌细胞的IC 50值分别为0.06-3.64μM和0.04-9.80μM。它们的抗增殖活性明显优于5-氟尿嘧啶（IC 50：56.96–174.50μM），并且接近于紫杉醇（IC 50）。：0.026–1.53μM）。这些衍生物的活性比查耳酮类似物（licochalcone A）的其他报道的结构高出100倍以上。初步的机理研究表明，这些化合物可抑制p53-MDM2的结合。在患有结肠癌HCT116细胞的BALB / c小鼠中，化合物A 1，A 7和A 9有效抑制肿瘤生长。该小组服用了200 mg / kg的化合物A 7在高剂量下显示出74.6％的肿瘤生长抑制作用，没有毒性迹象，这与12
• Design and Synthesis of Benzimidazole-Chalcone Derivatives as Potential Anticancer Agents
  作者：Hsieh、Ko、Chang、Kapoor、Liang、Lin、Horng、Hsu

  DOI：10.3390/molecules24183259

  日期：——

  Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing

  大量报道表明，共轭苯并咪唑衍生物具有多种生物活性，包括抗癌特性。在本报告中，我们设计并合成了 24 个新分子，包括苯并咪唑环、芳烃和带有烷基链的环状部分。结果表明，带有烷基链和含氮 5 或 6 元环的 N 取代苯并咪唑衍生物增强了对人乳腺癌 (MCF-7) 和人卵巢癌 (OVCAR-3) 细胞系的细胞毒作用. 在合成的 24 种化合物中，(2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2-yl)-3-phenyl-2-propen-1-one) (23a) 降低了 MCF 的增殖-7 和 OVCAR-3 细胞系显示出优于顺铂的结果。
• Treatment with low-dose sorafenib in combination with a novel benzimidazole derivative bearing a pyrolidine side chain provides synergistic anti-proliferative effects against human liver cancer
  作者：Ming-Hua Hsu、Shih-Ming Hsu、Yu-Cheng Kuo、Chih-Yu Liu、Cheng-Ying Hsieh、Yuh-Ching Twu、Chung-Kwe Wang、Yuan-Hsi Wang、Yi-Jen Liao

  DOI：10.1039/c6ra28281d

  日期：——

  Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and deadliest cancers in the world.

  肝细胞癌（HCC）是世界上最普遍的恶性肿瘤之一，也是最致命的癌症之一。
• Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1
  作者：Abhay Uthale、Aarti Anantram、Prasad Sulkshane、Mariam Degani、Tanuja Teni

  DOI：10.1007/s11030-022-10494-6

  日期：——

  Elevated expression of anti-apoptotic proteins, such as Bcl-2 and Mcl-1 contributes to poor prognosis and resistance to current treatment modalities in multiple cancers. Here, we report the design, synthesis and characterization of benzimidazole chalcone and flavonoid scaffold-derived bicyclic compounds targeting both Bcl-2 and Mcl-1 by optimizing the structural differences in the binding sites of both these proteins. Initial docking screen of Bcl-2 and Mcl-1 with pro-apoptotic protein Bim revealed possible hits with optimal binding energies. All the optimized bicyclic compounds were screened for their in vitro cytotoxic activity against two oral cancer cell lines (AW8507 and AW13516) which express high levels of Bcl-2 and Mcl-1. Compound 4d from the benzimidazole chalcone series and compound 6d from the flavonoid series exhibited significant cytotoxic activity (IC50 7.12 μM and 17.18 μM, respectively) against AW13516 cell line. Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) analysis further demonstrated that compound 4d and compound 6d could effectively inhibit the Bcl-2 and Mcl-1 proteins by displacing their BH3 binding partners. Both compounds exhibited potent activation of canonical pathway of apoptosis evident from appearance of cleaved Caspase-3 and PARP. Further, treatment of oral cancer cells with the inhibitors induced dissociation of the BH3 only protein Bim from Mcl-1 and Bak from Bcl-2 but failed to release Bax from Bcl-xL thereby confirming the nature of compounds as BH3-mimetics selectively targeting Bcl-2 and Mcl-1. Our study thus identifies bicyclic compounds as promising candidates for anti-apoptotic Bcl-2/Mcl-1 dual inhibitors with a potential for further development.

  抗凋亡蛋白（如Bcl-2和Mcl-1）的表达升高会导致多种癌症预后不良，并导致对现有治疗方式的耐药性。在此，我们报告了苯并咪唑查尔酮和黄酮类化合物骨架衍生物双环化合物的设计、合成和表征，这些化合物通过优化Bcl-2和Mcl-1结合位点的结构差异，同时靶向这两种蛋白。通过将Bcl-2和Mcl-1与促凋亡蛋白Bim进行初步对接筛选，我们发现了具有最佳结合能的可能的靶向化合物。对所有优化后的双环化合物进行了体外细胞毒性活性筛选，以检测其对两种表达高水平Bcl-2和Mcl-1的口腔癌细胞系（AW8507和AW13516）的细胞毒性活性。苯并咪唑查尔酮系列中的化合物4d和黄酮类化合物系列中的化合物6d对AW13516细胞系表现出显著的细胞毒性活性（IC50分别为7.12 μM和17.18 μM）。时间分辨荧光共振能量转移（TR-FRET）分析进一步表明，化合物4d和化合物6d可通过置换其BH3结合伴侣来有效抑制Bcl-2和Mcl-1蛋白。从裂解的Caspase-3