5-三氟甲基-1,3-二氢-苯并咪唑-2-酮 | 133687-93-1

• 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: 5-三氟甲基-1,3-二氢-苯并咪唑-2-酮
• 英文名称: 5-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
• 英文别名: 5-trifluoromethyl-1,3-dihydro-benzimidazol-2-one；5-(trifluoromethyl)-1H-benzo[d]imidazol-2(3H)-one；5-(trifluoromethyl)-1,3-dihydrobenzimidazol-2-one
• CAS: 133687-93-1
• 化学式: C₈H₅F₃N₂O
• 分子量: 202.136
• InChiKey: LSOWBXYANGMSPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-三氟甲基-1,3-二氢-苯并咪唑-2-酮 在 sodium hydride 、 caesium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (2R)-2-[2-chloro-5-[[3-(4-chlorobenzyl)-2-oxo-6-trifluoromethylbenzimidazol-1-yl]methyl]phenoxy]propanoic acid
  参考文献：
  名称：

  Benzimidazolones: A New Class of Selective Peroxisome Proliferator-Activated Receptor γ (PPARγ) Modulators

  摘要：

  A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR gamma modulators (SPPAR gamma Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR gamma full agonist drugs. Structure activity relationships of these potent and highly selective SPPAR gamma Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray aystallographic analysis, PPAR gamma transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR gamma receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (Si) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR gamma full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.

  DOI：

  10.1021/jm201061j
• 作为产物：
  描述：

  N,N'-羰基二咪唑 、 3,4-二胺基苄氧基三氟化物 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以73%的产率得到5-三氟甲基-1,3-二氢-苯并咪唑-2-酮
  参考文献：
  名称：

  通过虚拟筛选发现选择性Aurora A激酶抑制剂

  摘要：

  在这里，我们报告发现了Aurora A选择性抑制剂的发现，Aurora A是细胞分裂和潜在抗癌靶标的关键调节剂。我们使用原子类别扩展配体重叠评分（xLOS），这是我们小组最近开发的一种基于3D配体的虚拟筛选方法，用于选择437种参考激酶抑制剂的形状和药效基团类似物。生化筛选发现了两个激酶抑制剂系列中空前的支架抑制剂系列。其中一种已通过基于结构的设计成功优化为有效的Aurora A抑制剂（IC 50= 2 nM），对Aurora激酶具有非常高的激酶组选择性。该抑制剂将Aurora A锁定为非活性构象，并破坏与其激活蛋白TPX2的结合，从而削弱Aurora A在有丝分裂纺锤体上的定位并诱导细胞分裂缺陷。该表型可以通过抗抑制剂的Aurora A突变体挽救。此外，该抑制剂在细胞中不诱导Aurora B特异性作用。

  DOI：

  10.1021/acs.jmedchem.6b00709

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZIMIDAZOLES ET UTILISATION DE CEUX-CI EN TANT QUE LIGANDS DU RECEPTEUR VANILLOIDE
  申请人：AMGEN INC

  公开号：WO2004035549A1

  公开（公告）日：2004-04-29

  Compounds of formula (I) are useful in the treatment of vanilloid-receptor-meditated diseases, such as inflammatory or neuropathic pain and diseases involving sensory nerve function such as asthma, rheumatoid arthritis, osteoarthritis, inflammatory bowel disorders, urinary incontinence, migraine and psoriasis.

  式（I）的化合物在治疗辣椒素受体介导的疾病方面很有用，如炎症性或神经病痛以及涉及感觉神经功能的疾病，如哮喘、类风湿性关节炎、骨关节炎、炎症性肠道疾病、尿失禁、偏头痛和牛皮癣。
• [EN] QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF<br/>[FR] COMPOSÉS QUINAZOLINONES ET LEURS DÉRIVÉS
  申请人：AMGEN INC

  公开号：WO2014036022A1

  公开（公告）日：2014-03-06

  Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是坦克酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• Selenium‐Catalyzed Carbonylative Synthesis of 2‐Benzimidazolones from 2‐Nitroanilines with TFBen as the CO Source
  作者：Xinxin Qi、Rong Zhou、Jin‐Bao Peng、Jun Ying、Xiao‐Feng Wu

  DOI：10.1002/ejoc.201801739

  日期：2019.9

  A selenium‐catalyzed carbonylative reaction for the synthesis of 2‐benzimidazolones from 2‐nitroanilines has been developed. In this strategy, to avoid the usage of toxic CO gas, TFBen (benzene‐1,3,5‐triyl triformate) was used as a solid and stable CO precursor, and a variety of desired 2‐benzimidazolones were produced in moderate to excellent yields.

  已开发了一种硒催化的羰基化反应，用于从2-硝基苯胺合成2-苯并咪唑酮。在此策略中，为避免使用有毒的CO气体，TFBen（苯-1,3,5-三甲酸酯三甲酸酯）被用作固体和稳定的CO前体，并且生产了各种所需的2-苯并咪唑酮，其中中等至极好。产量。
• Direct, Metal-Free Amination of Heterocyclic Amides/Ureas with NH-Heterocycles and N-Substituted Anilines in POCl₃
  作者：Xiaohu Deng、Armin Roessler、Ivana Brdar、Roger Faessler、Jiejun Wu、Zachary S. Sales、Neelakandha S. Mani

  DOI：10.1021/jo201425q

  日期：2011.10.21

  A POCl3-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.

  描述了POCl 3介导的杂环酰胺/脲与NH-杂环或N-取代的苯胺的直接胺化反应。与现有方法相比，该操作简单的协议由于无金属的酸性反应条件，提供了独特的反应性和官能团兼容性。产量通常是极好的。
• NOVEL BENZIMIDAZOLE DERIVATIVE AND USE THEREOF
  申请人：HYOGO COLLEGE OF MEDICINE

  公开号：US20150011600A1

  公开（公告）日：2015-01-08

  The present invention aims to provide a compound capable of inhibiting PCA-1 that can be a target for a novel treatment method of various diseases, and pharmaceutical use of the compound. A compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof.

  本发明旨在提供一种能够抑制PCA-1的化合物，该化合物可作为各种疾病的新型治疗方法的靶点，并且可用于制药的该化合物。一种由以下化学式（I）表示的化合物：其中每个符号如描述中定义的，或其药用盐。