3-(3-bromo-phenyl)-4H-[1,2,4]oxadiazol-5-one | 26904-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-bromo-phenyl)-4H-[1,2,4]oxadiazol-5-one
• 英文别名: 3-(3-Bromophenyl)-4,5-dihydro-1,2,4-oxadiazol-5-one；3-(3-bromophenyl)-4H-1,2,4-oxadiazol-5-one
• CAS: 26904-01-8
• 化学式: C₈H₅BrN₂O₂
• mdl: MFCD12774154
• 分子量: 241.044
• InChiKey: WUSUENNDIGIWCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-bromo-phenyl)-4H-[1,2,4]oxadiazol-5-one 在 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 4-(4-{[3-(3-bromophenyl)-5-oxo-1,2,4-oxadiazol-4(5H)-yl]methyl}-1H-1,2,3-triazol-1-yl)benzoic acid
  参考文献：
  名称：

  Discovery of novel heterocyclic derivatives containing oxadiazolone or pyrimidinone cores as DPP‐4 inhibitors

  摘要：

  Type 2 diabetes is a chronic disease characterized by insulin resistance and alterations in incretin secretion, such as the glucagon‐like peptide‐1 (GLP‐1) hormone. GLP‐1 plays a crucial role in signaling insulin production in the pancreas, with its activity regulated by the dipeptidyl peptidase 4 (DPP‐4) enzyme. DPP‐4 presents an intriguing strategy for controlling type 2 diabetes. This study focuses on synthesizing 22 novel oxadiazolone and pyrimidinone derivatives, in vitro DPP‐4 inhibition, and elucidating binding modes through molecular docking simulations. Nine compounds showed promising inhibitory activity, with IC50 values ranging from 0.3 to 1.86 mM. Molecular docking simulations revealed interactions between these compounds and critical residues in the enzyme's active site, such as Arg125, Glu206, Ser630, and His740. This investigation introduces a new class of DPP‐4 inhibitors, providing insights into the design of more potent molecules as potential candidates for combating type 2 diabetes. The findings contribute to developing innovative therapeutics for managing this prevalent metabolic disorder.

  DOI：

  10.1002/jhet.4811
• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 生成 3-(3-bromo-phenyl)-4H-[1,2,4]oxadiazol-5-one
  参考文献：
  名称：

  Discovery of novel heterocyclic derivatives containing oxadiazolone or pyrimidinone cores as DPP‐4 inhibitors

  摘要：

  Type 2 diabetes is a chronic disease characterized by insulin resistance and alterations in incretin secretion, such as the glucagon‐like peptide‐1 (GLP‐1) hormone. GLP‐1 plays a crucial role in signaling insulin production in the pancreas, with its activity regulated by the dipeptidyl peptidase 4 (DPP‐4) enzyme. DPP‐4 presents an intriguing strategy for controlling type 2 diabetes. This study focuses on synthesizing 22 novel oxadiazolone and pyrimidinone derivatives, in vitro DPP‐4 inhibition, and elucidating binding modes through molecular docking simulations. Nine compounds showed promising inhibitory activity, with IC50 values ranging from 0.3 to 1.86 mM. Molecular docking simulations revealed interactions between these compounds and critical residues in the enzyme's active site, such as Arg125, Glu206, Ser630, and His740. This investigation introduces a new class of DPP‐4 inhibitors, providing insights into the design of more potent molecules as potential candidates for combating type 2 diabetes. The findings contribute to developing innovative therapeutics for managing this prevalent metabolic disorder.

  DOI：

  10.1002/jhet.4811

文献信息

• [EN] PYRIDINONE AND PYRIMIDINONE DERIVATIVES AS FACTOR XIA INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDINONE ET DE PYRIMIDINONE COMME INHIBITEURS DU FACTEUR XIA
  申请人：ONO PHARMACEUTICAL CO

  公开号：WO2013093484A1

  公开（公告）日：2013-06-27

  The present invention provides compounds of the general formula (I), their salts and N- oxides, and solvates and prodrugs thereof (wherein the characters are as defined in the description). The compounds of the general formula (I) are inhibitors of Factor XIa, so that they are useful in the prevention of and/or therapy for thromboembolic diseases.

  本发明提供了一般式(I)的化合物，它们的盐和N-氧化物，以及它们的溶剂合物和前药（其中字符如描述中所定义）。一般式(I)的化合物是因子XIa的抑制剂，因此它们在预防和/或治疗血栓栓塞疾病方面是有用的。
• Tuning chemoselectivity in <i>O</i>-/<i>N</i>-arylation of 3-aryl-1,2,4-oxadiazolones with <i>ortho</i>-(trimethylsilyl)phenyl triflates <i>via</i> aryne insertion
  作者：Lijing Zhou、Hongji Li、Wenge Zhang、Lei Wang

  DOI：10.1039/c8cc00124c

  日期：——

  A finely tunable chemoselectivity in arylation of 3-aryl-1,2,4-oxadiazolones with ortho-(trimethylsilyl)phenyl triflates is reported, including silver-catalysed O-arylation and metal-free N-arylation.

  报道了一种可以精细调节的化学选择性，用于将3-芳基-1,2,4-噁二唑酮与ortho-(三甲基硅基)苯基三氟甲磺酸酯进行芳基化反应，包括银催化的O-芳基化和无金属的N-芳基化。
• Tf₂NH-catalyzed formal [3 + 2] cycloaddition of oxadiazolones with ynamides: a simple access to aminoimidazoles
  作者：Yingying Zhao、Yancheng Hu、Xincheng Li、Boshun Wan

  DOI：10.1039/c7ob00701a

  日期：——

  Oxadiazolones are first employed as the three-atom coupling partners in the Tf2NH-catalyzed cycloaddition with ynamides. This formal [3 + 2] cycloaddition allows a rapid synthesis of aminoimidazoles with a broad substrate scope. The approach also features a metal-free catalytic cycloaddition process, which may find applications in the synthesis of bioactive molecules. Besides, the resulting N-methyl

  恶二唑酮首先用作Tf 2 NH催化的与酰胺类的环加成反应中的三原子偶联伙伴。这种正式的[3 + 2]环加成反应可快速合成具有广泛底物范围的氨基咪唑。该方法还具有无金属的催化环加成工艺，可在生物活性分子的合成中找到应用。此外，所得的N-甲基产物可以进一步容易地转化为游离的NH氨基咪唑。
• COMPOUNDS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20150152112A1

  公开（公告）日：2015-06-04

  The present invention provides compounds of the general formula (I), their salts and N-oxides, and solvates and prodrugs thereof (wherein the characters are as defined in the description). The compounds of the general formula (I) are inhibitors of Factor XIa, so that they are useful in the prevention of and/or therapy for thromboembolic diseases.

  本发明提供了一般式（I）的化合物，它们的盐和N-氧化物，以及它们的溶剂化物和前药（其中字符如描述中所定义）。一般式（I）的化合物是因子XIa的抑制剂，因此它们在预防和/或治疗血栓性疾病方面非常有用。
• Pyrimidinone and its derivatives inhibiting factor XIa
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US10717738B2

  公开（公告）日：2020-07-21

  The present invention provides compounds of the general formula (I), their salts and N-oxides, and solvates and prodrugs thereof (wherein the characters are as defined in the description). The compounds of the general formula (I) are inhibitors of Factor XIa, so that they are useful in the prevention of and/or therapy for thromboembolic diseases.

  本发明提供通式(I)化合物、其盐类和N-氧化物，以及其溶解物和原药（其中特征如描述中所定义）。通式（I）化合物是因子 XIa 的抑制剂，因此可用于预防和/或治疗血栓栓塞性疾病。