2-氯-5,6-二氟--1H-苯并咪唑 | 142356-63-6

• 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-氯-5,6-二氟--1H-苯并咪唑
• 中文别名: 2-氯-5,6-二氟-(9CI)-1H-苯并咪唑
• 英文名称: 2-Chloro-5,6-difulorobenzimidazole
• 英文别名: 2-Chloro-5,6-difluorobenzimidazole；2-chloro-5,6-difluoro-1H-1,3,-benzimidazole；2-chloro-5,6-difluoro-1H-benzo[d]imidazole；2-chloro-5,6-difluoro-1H-benzimidazole
• CAS: 142356-63-6
• 化学式: C₇H₃ClF₂N₂
• 分子量: 188.564
• InChiKey: VFELEJMYVUPGEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-5,6-二氟--1H-苯并咪唑 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 为溶剂， 反应 21.0h， 生成 5,6-difluoro-1-α-D-ribofuranosylbenzimidazole 2,2'-O-cyclonucleoside
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Evaluation of 2-Chloro-5,6-dihalo-1-β-d-ribofuranosylbenzimidazoles as Potential Agents for Human Cytomegalovirus Infections

  摘要：

  2-Chloro-5,6-difluorobenzimidazole (8) was prepared from 4,5-difluoro-2-nitroaniline (5) via successive reduction, cyclization, and diazotization reactions. 2-Chloro-5,6-dibromobenzimidazole (10) was obtained by a direct bromination of 2-chlorobenzimidazole (9) with bromine-water. 2-Chloro-5,6-diiodobenzimidazole (15) was synthesized by a stepwise transformation of the nitro functions of 2-chloro-5,6-dinitrobenzimidazole (11) into iodo groups via diazotization reactions. Ribosylation of 8, 10, and 15 gave the respective beta nucleosides 16a-c as the major products along with a small amount of the alpha anomers 17a-c. Deprotection of 16a-c afforded the corresponding free beta nucleo sides 2-chloro-5,6-difluoro-1-beta-D-ribofuranosylbenzimidazole (2), 2-chloro-5,D-dibromo-1-beta-D-ribofuranosylbenzimidazole (3), and 2-chloro-5,6-diiodo-1-beta-D-ribofuranosylbenzimidazole (4). Similar deprotection of the alpha anomers (17a-c) resulted in a removal of the acetyl protecting groups and a concomitant cyclization to give the 2,2'-O-cyclonucleosides (18a-c). Most of the benzimidazole heterocycles, but not the difluoro analog, were active against human cytomegalovirus (HCMV) (IC50's = 3-40 mu M) and herpes simplex virus type 1 (HSV-1) (IC50's = 50-90 mu M). This activity, however, was not well separated from cytotoxicity, IC50's = 10-100 mu M. The corresponding unsubstituted, the 5,6-dimethyl, and the 5,6-difluoro ribonucleosides (19, 20, and 2, respectively), were inactive against both viruses. Similar to the previously reported 2,5,6-trichloro analog (TCRB), the 5,6-dibromo ribonucleoside 3 was active against HCMV (IC50 approximate to 4 mu M) but more cytotoxic than TCRB. The 5,6-diiodo analog 4 also was active (IC50 approximate to 2 mu M) but more cytotoxic (IC50 = 10-20 mu M) than either 3 or TCRB. The cyclonucleosides were inactive against both viruses and not cytotoxic, or slightly active with corresponding cytotoxicity. The order of activity against HCMV of the dihalobenzimidazole ribonucleosides was I similar or equal to Br similar or equal to Cl much greater than F > H = CH3. The order of cytotoxicity among the most active compounds, however, was I > Br > Cl, thereby establishing that TCRB had the best antiviral properties.

  DOI：

  10.1021/jm960462g
• 作为产物：
  描述：

  5,6-二氟-1,3-二氢-2H-苯并咪唑-2-酮 在 三氯氧磷 作用下， 以88 %的产率得到2-氯-5,6-二氟--1H-苯并咪唑
  参考文献：
  名称：

  具有改善的药代动力学特性和抗癌功效的 SRC-3 抑制剂的先导化合物开发

  摘要：

  类固醇受体辅激活因子 3 (SRC-3) 是许多细胞内信号通路的关键介质，对癌症增殖和转移至关重要。在本研究中，我们在体外/体内代谢研究和细胞毒性测定的指导下，对热门化合物SI-2进行了构效关系探索和类药物优化。我们的努力发现了两种先导化合物： SI-10和SI-12 。两种化合物均对一组人类癌细胞系表现出有效的细胞毒性，并表现出可接受的药代动力学特性。生物素化雌激素反应元件下拉测定表明， SI-12可以破坏雌激素受体复合物中 SRC-3 和 p300 的募集。重要的是， SI-10和SI-12在体内显着抑制肿瘤生长和转移，且没有明显的急性毒性。这些结果证明了SI-10和SI-12作为癌症治疗候选药物的潜力，因为它们具有有效的 SRC-3 抑制作用以及有前景的药代动力学和毒性特征。

  DOI：

  10.1021/acs.jmedchem.3c01596

文献信息

• Preparation and use of aryl alkyl acid derivatives for the treatment of obesity
  申请人：Bayer Pharmaceuticals Corporation

  公开号：US20040224997A1

  公开（公告）日：2004-11-11

  This invention relates to certain aryl alkyl acid compounds, compositions, and methods for treating or preventing obesity and related diseases.

  这项发明涉及某些芳基烷基酸化合物、组合物以及治疗或预防肥胖和相关疾病的方法。
• [EN] BENZOIMIDAZOLES AS PROLYL HYDROXYLASE INHIBITORS<br/>[FR] BENZOIMIDAZOLES COMME INHIBITEURS DE LA PROLYL HYDROXYLASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009134750A1

  公开（公告）日：2009-11-05

  The present invention is directed to benzoimidazole compounds of the formula (1) and enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions modulated by prolyl hydroxylase activity.

  本发明涉及公式（1）的苯并咪唑化合物及其对映体、二对映体、消旋体和药学上可接受的盐。本发明的化合物在制药组合物和治疗由脯氨酸羟化酶活性调节的疾病状态、紊乱和条件的方法中是有用的。
• SMALL MOLECULE REGULATORS OF STEROID RECEPTOR COACTIVATORS AND METHODS OF USE THEREOF
  申请人：BAYLOR COLLEGE OF MEDICINE

  公开号：US20170290830A1

  公开（公告）日：2017-10-12

  Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.

  提供了小分子调节类固醇受体共激活子（SRC）家族蛋白的方法，以及它们在治疗或预防SRC相关疾病中的应用。SRC相关疾病可以包括癌症、代谢紊乱、人类免疫缺陷病毒、神经退行性疾病和/或炎症性疾病。还提供了在细胞中调节SRC家族蛋白的方法。
• Polysubstituted benzimidazoles as antiviral agents
  申请人：The Regents of the University of Michigan

  公开号：US05360795A1

  公开（公告）日：1994-11-01

  This invention relates to novel polysubstituted benzimidazoles and compositions and their use in the treatment of viral infections. The polysubstituted benzimidazoles and compositions of the present invention exhibit antiviral properties against viruses of the herpes family, particularly human cytomegalovirus (HCMV) and herpes simplex viruses (HSV). Preferred polysubstituted benzimidazoles of the invention are 2,5,6-Trichloro-1-(.beta.-D-5-deoxyribofuranosyl)benzimidazole and 2-bromo-5,6-dichloro-1-(5-deoxy-.beta.-D-ribofuranosyl)benzimidazole.

  这项发明涉及新型多取代苯并咪唑及其组合物，以及它们在治疗病毒感染中的用途。本发明的多取代苯并咪唑和组合物对疱疹病毒家族的病毒，特别是人类巨细胞病毒（HCMV）和单纯疱疹病毒（HSV）表现出抗病毒特性。该发明的首选多取代苯并咪唑是2,5,6-三氯-1-(β-D-5-脱氧核糖呋喃糖基)苯并咪唑和2-溴-5,6-二氯-1-(5-脱氧-β-D-核糖呋喃糖基)苯并咪唑。
• [EN] INDOLE/BENZIMIDAZOLE COMPOUNDS AS mTOR KINASE INHIBITORS<br/>[FR] COMPOSÉS D'INDOLE OU BENZIMIDAZOLE CONVENANT COMME INHIBITEURS DE LA KINASE MTOR
  申请人：AMGEN INC

  公开号：WO2010096314A1

  公开（公告）日：2010-08-26

  The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了一种激酶抑制剂化合物，具体来说是PIK激酶抑制剂，更具体地说是mTOR抑制剂，因此适用于治疗通过抑制激酶治疗的疾病，特别是PIK激酶抑制剂，更具体地说是mTOR抑制剂，例如癌症。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。