2-(三氯甲基)-苯并咪唑 | 3584-65-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-(三氯甲基)-苯并咪唑
• 中文别名: 1H-苯并咪唑,2-(三氯甲基)-；苯并咪唑,2-三氯甲基-；2-(三氯甲基)-1H-苯并咪唑；2-三氯甲基苯并咪唑
• 英文名称: 2-trichloromethyl-1H-benzoimidazole
• 英文别名: 2-trichloromethylbenzimidazole；2-(trichloromethyl)-1H-benzo[d]imidazole；2-(trichloromethyl)-1H-benzimidazole；(2-trichloromethyl-benzoimidazole)
• CAS: 3584-65-4
• 化学式: C₈H₅Cl₃N₂
• mdl: MFCD00022677
• 分子量: 235.5
• InChiKey: ZVFSYTFFWGYEMM-UHFFFAOYSA-N

物化性质

• 熔点：
  360 °C
• 沸点：
  346.9±42.0 °C(Predicted)
• 密度：
  1.608±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(三氯甲基)-苯并咪唑 在 氨 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 3.0h， 以76%的产率得到1H-苯并咪唑-2-甲腈
  参考文献：
  名称：

  发现新型苯并[4,5]咪唑并[1,2-a]吡嗪-1-胺-3-酰胺-酮衍生物作为抗癌人A2A腺苷受体拮抗剂

  摘要：

  A 2A腺苷受体 (A 2A AR) 的阻断通过调节肿瘤微环境中的信号传导来激活免疫刺激反应。因此，A 2A AR 已被提议作为癌症免疫治疗的有希望的靶标。在这项工作中，我们设计了一系列新的苯并[4,5]咪唑并[1,2 - a ]吡嗪-1-胺衍生物，在3位具有酰胺取代，以在体内获得有效的抗肿瘤拮抗剂。通过分子建模和放射性测定进行构效关系研究。通过3',5'-环磷酸腺苷 (cAMP) 功能和 T 细胞活化测定评估体外抗癌活性。最强的化合物12o·2HCl与临床拮抗剂 AZD4635 相比，对 A 2A AR ( K i = 0.08 nM) 显示出更高的亲和力，并表现出更显着的体外免疫刺激抗癌活性。更重要的是，12o·2HCl通过逆转异种移植小鼠模型中的免疫抑制性肿瘤微环境，显着抑制三阴性乳腺癌的生长，且在试验剂量下无严重毒性。这些结果使12o·2HCl成为一种很有前途的免疫治疗抗癌药物候选者。

  DOI：

  10.1021/acs.jmedchem.2c00101
• 作为产物：
  描述：

  2-硝基苯胺 在 盐酸 、 铁粉 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 生成 2-(三氯甲基)-苯并咪唑
  参考文献：
  名称：

  Synthesis of novel histamine H4 receptor antagonists

  摘要：

  This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.098
• 作为试剂：
  描述：

  1-tert-butyl 3-methyl 5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate 、 2-(三氯甲基)-苯并咪唑 在 2-(三氯甲基)-苯并咪唑 作用下， 以84的产率得到1-tert-butyl 3-methyl (3R,5S)-5-[(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino]piperidine-1,3-dicarboxylate
  参考文献：
  名称：

  ACS Med. Chem. Lett. 2016, 7, 933-938

  摘要：

  DOI：

文献信息

• [EN] METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016206101A1

  公开（公告）日：2016-12-29

  The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及一种属于金属β-内酰胺酶抑制剂的I式化合物，以及这种化合物的合成和将其与β-内酰胺类抗生素一起用于克服耐药性的用途。
• Experimental and QSAR Studies on Antimicrobial Activity of Benzimidazole Derivatives
  作者：Ayarivan Puratchikody、Govindasamy Nagalakshmi、Mukesh Doble

  DOI：10.1248/cpb.56.273

  日期：——

  Twenty eight analogues of benzimidazoles had been synthesized and tested for their antimicrobial activity against four bacteria (Staphylococcus auerus, Escherichia coli, Bacillus pumilus and Proteus vulgaris) and two fungi (Aspergillus flavus and Aspergilus niger). Compounds with R as C6H4NO2 and R′ as SO2C6H4–CH3(p), with R as C6H4OCH3 and R′ as SO2C6H4–CH3(p), and with R as CH2C6H5 and R′ as CH2(CH2)9Cl exhibited comparable or higher antibacterial activity than Ciprofloxacin against S. auerus and E. coli and, higher activity than Nystatin against A. flavus. Several other compounds showed better activity than the standard antibiotic for E. coli. Compounds with R as CCl3 and R′ as SO2C6H4–CH3(p) or COC6H5 exhibited the lowest activity against all the organisms. Addition of methylene groups in the R′ position increased activity. Many of the compounds showed better activity than Ciprofloxacin for one or more organisms. Compound with R as CH2OC6H5 and R′ as CH2(CH2)9Cl exhibited higher activity against both the fungii than the control Nystatin. Quantitative structure activity relationships (QSARs) developed were good for all the organisms (R2=0.65 to 0.88; Radj2 = 0.63 to 0.86) and the predictive capability of the developed models was also reasonable (q2=0.52 to 0.83). The models had two to three independent variables. The data for the models which had three independent variables were divided into training and test/validation sets. The former set was used to develop the QSAR and these developed models were used to predict the activity of the test set data. In all the three cases the predictive capability of the models was good. The molecular descriptors identified were predominantly log P, electronic parameters, molecular size, shape and area. A positive correlation existed between the antibacterial activity and the first principal component.

  已经合成了28种苯并咪唑类衍生物，并对它们对四种细菌（金黄色葡萄球菌、大肠杆菌、短小芽孢杆菌和普通变形杆菌）和两种真菌（黄曲霉和黑曲霉）的抗微生物活性进行了测试。当R为C6H4NO2、R′为SO2C6H4-CH3(p)，R为C6H4OCH3、R′为SO2C6H4-CH3(p)，以及R为CH2C6H5、R′为CH2(CH2)9Cl时，这些化合物的抗菌活性与环丙沙星相当或更高，对金黄色葡萄球菌和大肠杆菌的活性高于制霉菌素对黄曲霉的活性。还有几种化合物对大肠杆菌的活性优于标准抗生素。R为CCl3、R′为SO2C6H4-CH3(p)或COC6H5的化合物对所有生物体的活性最低。在R′位置添加亚甲基基团可以提高活性。许多化合物对一种或多种生物体的活性优于环丙沙星。R为CH2OC6H5、R′为CH2(CH2)9Cl的化合物对这两种真菌的活性高于对照制霉菌素。开发的定量结构-活性关系（QSARs）对所有生物体都很好（R2=0.65至0.88；Radj2 = 0.63至0.86），开发模型的预测能力也合理（q2=0.52至0.83）。这些模型包含两到三个独立变量。具有三个独立变量的模型的数据被分为训练集和测试/验证集。前者用于开发QSAR，这些开发的模型用于预测测试集数据的活性。在所有三种情况下，模型的预测能力都很好。识别的分子描述符主要是log P、电子参数、分子大小、形状和面积。抗菌活性与第一主成分之间存在正相关关系。
• Design, synthesis and biological evaluation of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine: Towards adenosine A2A receptor (A2A AR) antagonist
  作者：G. Lakshma Reddy、Rupam Sarma、Shuhao Liu、Weifeng Huang、Jinping Lei、Jiasheng Fu、Wenhao Hu

  DOI：10.1016/j.ejmech.2020.113040

  日期：2021.1

  Antagonists of adenosine receptor are under exploration as potential drug candidates for treatment of neurological disorders, depression, certain cancers and potentially used as a cancer immunotherapy. Herein, we describe design and synthesis of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine (6) derivatives. All the compounds were evaluated for A2A AR antagonist activity and displayed encouraging

  腺苷受体的拮抗剂正在探索作为治疗神经系统疾病，抑郁症，某些癌症的潜在候选药物，并有可能用作癌症免疫疗法。在这里，我们描述了新型支架苯并[4,5]咪唑并[1,2 - a ]吡嗪-1-胺（6）衍生物的设计和合成。对所有化合物的A 2A AR拮抗剂活性进行了评估，并在生化分析中显示出令人鼓舞的A 2A AR拮抗剂结合亲和力结果（IC 50 9–300 nM）。化合物27在A 2A AR拮抗剂cAMP功能测定（IC 5031 nM），并且该化合物在IL-2产生试验（EC 50 165 nM）时显示T细胞活化。进行了分子对接研究以合理化所观察到的化合物27的结合亲和力。
• [EN] NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS<br/>[FR] COMPOSÉS AZOTÉS HÉTÉROCYCLIQUES CONVENANT COMME INHIBITEURS DE LA PDE10
  申请人：AMGEN INC

  公开号：WO2011143365A1

  公开（公告）日：2011-11-17

  Unsaturated nitrogen heterocyclic compounds of formula (I): (I), as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  式(I)的不饱和氮杂环化合物：(I)，如规范中定义的，含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10治疗可治疗的疾病或疾病的方法，如肥胖症、亨廷顿病、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症等。
• AZA-HETEROARYL COMPOUNDS AS PI3K-GAMMA INHIBITORS
  申请人：Incyte Corporation

  公开号：US20160229843A1

  公开（公告）日：2016-08-11

  The present invention provides aza-heteroaryl derivatives of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R 4 , R 5 , and R 6 are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.

  本发明提供了式I的氮杂杂环衍生物及其药学上可接受的盐，其中X、Y、Z、A、W、R4、R5和R6在此处定义，并且抑制磷脂酰肌醇3-激酶γ（PI3Kγ）的活性，并且在治疗与PI3Kγ活性相关的疾病方面具有用处，例如自身免疫疾病、癌症、心血管疾病和神经退行性疾病。