2-(3,4-dichlorophenyl)-5-nitro-1H-benzo[d]imidazole | 99585-47-4

• 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: 2-(3,4-dichlorophenyl)-5-nitro-1H-benzo[d]imidazole
• 英文别名: 2-(3,4-Dichlorophenyl)-5-nitrobenzimidazole；2-(3,4-dichlorophenyl)-6-nitro-1H-benzimidazole
• CAS: 99585-47-4
• 化学式: C₁₃H₇Cl₂N₃O₂
• 分子量: 308.123
• InChiKey: MMZGYWJDPXSKOG-UHFFFAOYSA-N

物化性质

• 沸点：
  535.4±60.0 °C(Predicted)
• 密度：
  1.571±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 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：
  74.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3,4-dichlorophenyl)-5-nitro-1H-benzo[d]imidazole 在 铁粉 、 溶剂黄146 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 7.0h， 生成 N-(2-(2-bromo-5-fluorophenyl)-1H-benzo[d]imidazol-6-yl)quinazolin-4-amine
  参考文献：
  名称：

  Discovery of quinazolin-4-amines bearing benzimidazole fragments as dual inhibitors of c-Met and VEGFR-2

  摘要：

  Both c-Met and VEGFR-2 are important targets for the treatment of cancers. In this study, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinazolin-4-amine derivatives were designed and identified as dual c-Met and VEGFR-2 inhibitors. Among these compounds bearing quinazoline and benzimidazole fragments, compound 7j exhibited the most potent inhibitory activity against c-Met and VEGFR-2 with IC50 of 0.05μM and 0.02μM, respectively. It also showed the highest anticancer activity against the tested cancer cell lines with IC50 of 1.5μM against MCF-7 and 8.7μM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, which demonstrates that compound 7j is a potential agent for cancer therapy deserving further researching.

  DOI：

  10.1016/j.bmc.2014.07.008
• 作为产物：
  描述：

  3,4-二氯苯甲酸 、 4-硝基邻苯二胺 在 polyphosphoric acid (PPA) 作用下， 反应 5.0h， 以42%的产率得到2-(3,4-dichlorophenyl)-5-nitro-1H-benzo[d]imidazole
  参考文献：
  名称：

  的发现ñ - （2-苯基- 1 H ^ -苯并[ d ]咪唑-5-基）喹啉-4-胺衍生物是新颖的VEGFR-2激酶抑制剂

  摘要：

  抑制VEGF信号传导途径已成为治疗癌症的有价值的方法。在这项工作中，设计了一系列N-（2-苯基-1 H-苯并[ d ]咪唑-5-基）喹啉-4-胺衍生物并将其鉴定为VEGFR-2（KDR）激酶的有效抑制剂。合成了具有喹啉骨架和苯并咪唑部分的这些化合物，并评估了它们对VEGFR-2和两种人类癌细胞系的生物学活性。其中，化合物7s对VEGFR-2的抑制作用最强，IC 50为0.03μM，对受试癌细胞系的IC 50表现出最高的抗癌活性。针对MCF-7为1.2μM，针对Hep-G2为13.3μM。对接模拟支持最初的药效学假说，并提出了在VEGFR-2 ATP结合位点的共同相互作用方式，这表明化合物7s是潜在的癌症治疗药物，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2014.07.071

文献信息

• Novel anti-inflammatory and analgesic heterocyclic amidines that inhibit nitrogen oxide (NO) production
  申请人：Makovec Francesco

  公开号：US20050197331A1

  公开（公告）日：2005-09-08

  Heterocyclic amidines with anti-inflammatory and analgesic activity that inhibit nitrogen oxide production, of formula (I): in which: G 1 and G 2 are hydrogen, halogen, hydroxyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, and an amidino substituent of formula Q, provided that, for each compound of formula (I), only one of the two substituents G 1 or G 2 is an amidino substituent of formula Q: and in which the substituents W, Y and X are combined to form 9- or 10-membered bicyclic heteroaromatic derivatives containing up to 2 hetero atoms in the same ring; and Z is an aryl or heteroaryl group, a linear or branched C 1 -C 6 alkyl or alkenyl chain, a C 1 -C 4 alkyl-aryl group or a C 1 -C 4 alkyl-heteroaryl group.

  含有抗炎和镇痛活性、抑制氮氧化物产生的杂环胺基化合物，化学式（I）如下：其中：G1和G2为氢、卤素、羟基、C1-C4烷氧基、C1-C4烷基和式为Q的胺基取代基，但对于化合物的每个化学式（I），G1或G2中仅有一个是式为Q的胺基取代基；其中取代基W、Y和X结合形成含有最多2个杂原子的同一环中的9-或10-成员双环杂芳衍生物；Z为芳基或杂芳基团、线性或支链状的C1-C6烷基或烯基链、C1-C4烷基-芳基团或C1-C4烷基-杂芳基团。
• Novel Anti-Inflammatory and Analgesic Heterocyclic Amidines that Inhibit Nitrogen Oxide (NO) Production
  申请人：MAKOVEC Francesco

  公开号：US20100120802A1

  公开（公告）日：2010-05-13

  Heterocyclic amidines with anti-inflammatory and analgesic activity that inhibit nitrogen oxide production, of formula (I): in which: G 1 and G 2 are hydrogen, halogen, hydroxyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, and an amidino substituent of formula Q, provided that, for each compound of formula (I), only one of the two substituents G 1 or G 2 is an amidino substituent of formula Q: and in which the substituents W, Y and X are combined to form 9- or 10-membered bicyclic heteroaromatic derivatives containing up to 2 hetero atoms in the same ring; and Z is an aryl or heteroaryl group, a linear or branched C 1 -C 6 alkyl or alkenyl chain, a C 1 -C 4 alkyl-aryl group or a C 1 -C 4 alkyl-heteroaryl group.

  具有抗炎和镇痛活性，能够抑制氮氧化物产生的杂环胺基化合物，化学式为（I）：其中：G1和G2是氢，卤素，羟基，C1-C4烷氧基，C1-C4烷基和公式Q的氨基甲基取代基，只有公式（I）中的两个取代基G1或G2中的一个是公式Q的氨基甲基取代基；其中取代基W，Y和X组合形成含有最多2个杂原子的9-或10成员双环杂芳基衍生物；Z是芳基或杂芳基基团，线性或分支的C1-C6烷基或烯基链，C1-C4烷基芳基基团或C1-C4烷基杂芳基基团。
• Design, synthesis, bio-evaluation, and <i>in silico</i> studies of some N-substituted 6-(chloro/nitro)-1<i>H</i>-benzimidazole derivatives as antimicrobial and anticancer agents
  作者：Em Canh Pham、Tuong Vi Thi Le、Tuyen Ngoc Truong

  DOI：10.1039/d2ra03491c

  日期：——

  A new series of 6-substituted 1H-benzimidazole derivatives were synthesized by reacting various substituted aromatic aldehydes with 4-nitro-o-phenylenediamine and 4-chloro-o-phenylenediamine through condensation using sodium metabisulfite as the oxidative reagent. The N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives were prepared from the 6-substituted 1H-benzimidazole derivatives and substituted

  以焦亚硫酸钠为氧化试剂，将各种取代芳香醛与4-硝基邻苯二胺、4-氯邻苯二胺进行缩合反应，合成了一系列新的6-取代1H-苯并咪唑衍生物。 N-取代的6-(氯/硝基)-1H-苯并咪唑衍生物由6-取代的1H-苯并咪唑衍生物和取代的卤化物使用碳酸钾通过常规方法以及通过暴露于微波辐射来制备。采用微波辅助方法合成了 76 种 1 H -苯并咪唑衍生物，产率中等至优异（40% 至 99%）。化合物1d 、 2d 、 3s 、 4b和4k对大肠杆菌、粪链球菌、MSSA（甲氧西林敏感金黄色葡萄球菌菌株）和 MRSA（耐甲氧西林金黄色葡萄球菌菌株）表现出有效的抗菌活性，具有 MIC（最小抑制）与环丙沙星 (MIC = 8–16 μg mL -1 ) 相比，化合物 4k 在 2 至 16 μg mL -1之间，特别是化合物4k对白色念珠菌和黑曲霉表现出有效的真菌活性，MIC 范围在 8 至 16 μg mL -1
• Synthesis and<i>In Vitro</i>Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents
  作者：Hakan Göker、Cigdem Karaaslan、Mustafa Orhan Püsküllü、Sulhiye Yildiz、Yalcin Duydu、Aylin Üstündağ、Can Özgür Yalcin

  DOI：10.1111/cbdd.12623

  日期：2016.1

  A series of novel polyhalogenated 2‐phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug‐resistant bacterial strains (methicillin‐resistant Staphylococcus aureus, and vancomycin‐resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 μg/mL) with the lowest MIC values with 0.19 μg/mL against methicillin‐resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin‐resistant Enterococcus faecium (1.56 μg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti‐methicillin‐resistant Staphylococcus aureus and anti‐vancomycin‐resistant Enterococcus faecium agents.
• 6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure–activity relationship
  作者：K.M. Khan、Zarbad Shah、V.U. Ahmad、N. Ambreen、M. Khan、M. Taha、F. Rahim、S. Noreen、S. Perveen、M.I. Choudhary、W. Voelter

  DOI：10.1016/j.bmc.2011.12.041

  日期：2012.2

  6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC50 values between 1.5 +/- 0.043 and 294.0 +/- 16.7 mu M. Compounds 30 (IC50 = 1.5 +/- 0.043 mu M), 1 (IC50 = 2.4 +/- 0.049 mu M), 11 (IC50 = 5.7 +/- 0.113 mu M), 13 (IC50 = 6.4 +/- 0.148 mu M), 14 (IC50 = 10.5 +/- 0.51 mu M), 9 (IC50 = 11.49 +/- 0.08 mu M), 3 (IC50 = 63.1 +/- 1.48 mu M), 10 (IC50 = 120.0 +/- 4.47 mu M), and 6 (IC50 = 153.2 +/- 5.6 mu M) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC50 = 274 +/- 0.007 mu M), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. Astructure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters (C) 2011 Elsevier Ltd. All rights reserved.