2-(furan-2-yl)-5-methoxy-1H-benzo[d]imidazole

• 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-(furan-2-yl)-5-methoxy-1H-benzo[d]imidazole
• 英文别名: 2-(furan-2-yl)-6-methoxy-1H-benzimidazole
• 化学式: C₁₂H₁₀N₂O₂
• 分子量: 214.224
• InChiKey: VNHCPMJAAWFRSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  silver(II) nitrate 、 2-(furan-2-yl)-5-methoxy-1H-benzo[d]imidazole 以 二甲基亚砜 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  使用Ag +-苯并咪唑配合物开发用于汗液中氯离子检测的荧光化学传感器

  摘要：

  汗液中的氯离子（Cl +）水平是遗传性疾病囊性纤维化（CF）的公认生物标志物。因此，对汗液中氯离子的准确定量是这种威胁生命的疾病的重要诊断工具。在这项工作中，通过利用银（Ag +）与氯离子之间的强相互作用，开发了一种荧光的氯离子化学传感器。使用配体置换的概念，制备了六个Ag +-苯并咪唑配合物作为候选氯离子化学传感器。银+ -2-（呋喃-2-基）-1- ħ -苯并[ d ]咪唑（银+ - FBI）络合物被鉴定为由于其银的最佳传感器+ -FBI灵敏度高（检测极限= 19μM），响应时间短（<3分钟），在宽pH范围（pH 6–9）中均具有显着的荧光开启响应。银+ - FBI复杂表现出高的对的Cl -离子和选择性被成功地用于含有多个离子和其它生物成分人工汗液样品中进行量化氯离子。因此，这种独特，简单而有效的探针在临床诊断应用中显示出巨大的潜力。

  DOI：

  10.1016/j.dyepig.2020.108291
• 作为产物：
  描述：

  2-呋喃甲胺 、 4-氟-3-硝基苯甲醚 在 N-甲基吡咯烷酮 、 potassium carbonate 作用下， 反应 4.0h， 以76%的产率得到2-(furan-2-yl)-5-methoxy-1H-benzo[d]imidazole
  参考文献：
  名称：

  取代苯并吡啶稠合 1H-咪唑的一步合成

  摘要：

  摘要 取代的苯并咪唑类和嘧唑类化合物是药物化学领域中一类重要的杂环芳香族有机化合物。已经描述了取代苯并和吡啶稠合的 1H-咪唑的一步微波加速合成。从机理上讲，该反应通过取代的 2-氟硝基苯和取代的芳基胺通过形成 N-羟基中间体进行反应，该中间体在较高温度下裂解得到所需的产物。与先前描述的合成方法相比，这种方法实现了反应时间的减少、更高的产率、更清洁的反应。

  DOI：

  10.1080/00397911.2021.2001658

文献信息

• [EN] CANCER THERAPEUTICS<br/>[FR] TRAITEMENTS ANTICANCÉREUX
  申请人：UNIV VIRGINIA PATENT FOUND

  公开号：WO2016025744A1

  公开（公告）日：2016-02-18

  This invention relates to compounds that bind to wild-type CBFβ and inhibit CBFβ binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBFβ from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBFβ in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention. In one embodiment, the cancer is selected from the group consisting of a RUNX-signaling-dependent leukemia that expresses wild-type CBFβ, lung cancer, bladder cancer, ovarian cancer, uterine cancer, endometrial cancer, breast cancer, liver cancer, pancreatic cancer, stomach cancer, cervical cancer, lymphoma, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, salivary gland cancer, bone cancer, brain cancer, colon cancer, rectal cancer, colorectal cancer, kidney cancer, skin cancer, melanoma, squamous cell carcinoma of the tongue, pleomorphic adenoma, hepatocellular carcinoma, pancreatic cancer, squamous cell carcinoma, and/or adenocarcinoma. In another embodiment, the compounds of the invention can be used to treat a leukemia, lung cancer, ovarian cancer, and/or breast cancer.

  本发明涉及与野生型CBFβ结合并抑制CBFβ与RUNX蛋白结合的化合物。本发明的有效化合物以低微摩尔浓度抑制这种蛋白质-蛋白质相互作用，利用变构机制实现抑制，从细胞中置换野生型CBFβ从而改变RUNX1在靶基因上的占位率，改变RUNX1靶基因的基因表达。这些抑制剂表现出与靶向RUNX蛋白活性一致的明显生物学效应。含有本发明化合物和药学可接受载体的制药组合物代表该发明的另一实施形式。该发明的另一实施形式是通过向需要治疗的主体施用本发明化合物的治疗有效量来治疗表达野生型CBFβ的RUNX信号依赖性癌症。在一种实施形式中，该癌症被选自RUNX信号依赖性白血病，肺癌，膀胱癌，卵巢癌，子宫癌，子宫内膜癌，乳腺癌，肝癌，胰腺癌，胃癌，宫颈癌，淋巴瘤，白血病，急性髓性白血病，急性淋巴细胞白血病，涎腺癌，骨癌，脑癌，结肠癌，直肠癌，结直肠癌，肾癌，皮肤癌，黑色素瘤，舌鳞状细胞癌，多形性腺瘤，肝细胞癌，胰腺癌，鳞状细胞癌和/或腺癌。在另一实施形式中，本发明的化合物可用于治疗白血病，肺癌，卵巢癌和/或乳腺癌。
• IMIDAZOLE DERIVATIVES HAVING ARYL PIPERIDINE SUBSTITUENT, METHOD FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
  申请人：Suh Jee Hee

  公开号：US20100145054A1

  公开（公告）日：2010-06-10

  The present invention is directed to a novel imidazole derivative having an aryl piperidine substituent of formula (I) and a method for preparation thereof, and a pharmaceutical composition containing said imidazole derivative as an active ingredient for preventing or treating a MCH (melanine-concentrating hormone)-related disease.

  本发明涉及一种具有式(I)的芳基哌啶取代基的新型咪唑衍生物及其制备方法，以及含有该咪唑衍生物作为活性成分的药物组合物，用于预防或治疗与MCH（黑色素浓集激素）相关的疾病。
• Atroposelective Chan–Evans–Lam Amination
  作者：Vinzenz Thönnißen、Johannes Westphäling、Iuliana L. Atodiresei、Frederic W. Patureau

  DOI：10.1002/chem.202304378

  日期：2024.3.15

  The synthetic control of atropoisomerism along C−N bonds is a major challenge, and methods that allow C−N atroposelective bond formation are rare. This is a problem because each atropoisomer can feature starkly differentiated biological properties. Yet, among the three most practical and applicable classical amination methods available: 1) the Cu‐catalyzed Ullmann–Goldberg reaction, 2) the Pd‐catalyzed Buchwald–Hartwig reaction, and 3) the Cu‐catalyzed Chan–Evans–Lam reaction, none has truly been rendered atroposelective at the newly formed C−N bond. The first ever Chan–Evans–Lam atroposelective amination is herein described with a simple copper catalyst and newly designed PyrOx chiral ligand. This method should find important applications in asymmetric synthesis, in particular for medicinal chemistry.

  摘要 对 C-N 键的异构体进行合成控制是一项重大挑战，而能够形成 C-N 异选择性键的方法却很少见。这是一个问题，因为每种异构体都可能具有截然不同的生物特性。然而，在现有的三种最实用、最适用的经典胺化方法中1) Cu 催化的 Ullmann-Goldberg 反应；2) Pd 催化的 Buchwald-Hartwig 反应；3) Cu 催化的 Chan-Evans-Lam 反应，但没有一种能真正在新形成的 C-N 键上实现异选择性。本文利用简单的铜催化剂和新设计的 PyrOx 手性配体，首次描述了 Chan-Evans-Lam 无选择性胺化反应。这种方法将在不对称合成，特别是药物化学中得到重要应用。
• Cancer therapeutics
  申请人：UNIVERSITY OF VIRGINIA PATENT FOUNDATION

  公开号：US10562890B2

  公开（公告）日：2020-02-18

  This invention relates to compounds that bind to wild-type CBFβ and inhibit CBFβ binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBFβ from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBFβ in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention. In one embodiment, the cancer is selected from the group consisting of a RUNX-signaling-dependent leukemia that expresses wild-type CBFβ, lung cancer, bladder cancer, ovarian cancer, uterine cancer, endometrial cancer, breast cancer, liver cancer, pancreatic cancer, stomach cancer, cervical cancer, lymphoma, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, salivary gland cancer, bone cancer, brain cancer, colon cancer, rectal cancer, colorectal cancer, kidney cancer, skin cancer, melanoma, squamous cell carcinoma of the tongue, pleomorphic adenoma, hepatocellular carcinoma, pancreatic cancer, squamous cell carcinoma, and/or adenocarcinoma. In another embodiment, the compounds of the invention can be used to treat a leukemia, lung cancer, ovarian cancer, and/or breast cancer.

  本发明涉及与野生型 CBFβ 结合并抑制 CBFβ 与 RUNX 蛋白结合的化合物。本发明的强效化合物可在低微摩尔浓度下抑制这种蛋白-蛋白相互作用，利用异构机制实现抑制作用，将细胞中的野生型 CBFβ 从 RUNX1 中置换出来，改变 RUNX1 对靶基因的占有率，并改变 RUNX1 靶基因的基因表达。这些抑制剂显示出与靶上 RUNX 蛋白活性一致的明显生物效应。含有本发明化合物和药学上可接受的载体的药物组合物代表了本发明的另一个实施方案。本发明的另一个实施方案是通过向有需要的受试者施用治疗有效量的本发明化合物来治疗表达野生型 CBFβ 的 RUNX 信号依赖性癌症的方法。在一个实施方案中，所述癌症选自由表达野生型 CBFβ 的 RUNX 信号依赖性白血病、肺癌、膀胱癌、卵巢癌、子宫癌、子宫内膜癌、乳腺癌、肝癌、胰腺癌、胃癌、宫颈癌、淋巴瘤、白血病、急性髓性白血病、急性淋巴细胞白血病、急性淋巴细胞白血病、急性髓细胞白血病、急性淋巴细胞白血病、唾液腺癌、骨癌、脑癌、结肠癌、直肠癌、结直肠癌、肾癌、皮肤癌、黑色素瘤、舌鳞癌、多形性腺瘤、肝细胞癌、胰腺癌、鳞状细胞癌和/或腺癌。在另一个实施方案中，本发明的化合物可用于治疗白血病、肺癌、卵巢癌和/或乳腺癌。
• CANCER THERAPEUTICS
  申请人：University Of Virginia Patent Foundation

  公开号：EP3180004B1

  公开（公告）日：2021-01-06