3-amino-5-phenylbenzofuran-2-carboxamide | 1380495-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-amino-5-phenylbenzofuran-2-carboxamide
• 英文别名: 3-Amino-5-phenyl-2-benzofurancarboxamide；3-amino-5-phenyl-1-benzofuran-2-carboxamide
• CAS: 1380495-98-6
• 化学式: C₁₅H₁₂N₂O₂
• 分子量: 252.272
• InChiKey: LIJPOGVRZOHJKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  486.1±40.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-5-phenylbenzofuran-2-carboxamide 、 2-氯苯甲醛 生成 2-(2-chlorophenyl)-8-phenyl-3H-[1]benzofuro[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  The design, synthesis, and biological evaluation of PIM kinase inhibitors

  摘要：

  A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.025
• 作为产物：
  描述：

  2-((3-cyano-[1,1'-biphenyl]-4-yl)oxy)acetamide 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-amino-5-phenylbenzofuran-2-carboxamide
  参考文献：
  名称：

  The design, synthesis, and biological evaluation of PIM kinase inhibitors

  摘要：

  A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.025

文献信息

• [EN] BENZOFURAN DERIVATIVES FOR USE AS AMPK ACTIVATORS<br/>[FR] DÉRIVÉS DE BENZOFURANE DESTINÉS À ÊTRE UTILISÉS EN TANT QU'ACTIVATEURS D'AMPK
  申请人：UNIV PISA

  公开号：WO2018189683A1

  公开（公告）日：2018-10-18

  The present invention refers to benzofuran derivatives, capable of efficaciously activating the enzymatic complex AMPK, useful for the prophylaxis and therapeutic treatment of diseases and disorders in particular metabolic disorders such as diabetes and obesity, immune-mediated inflammatory pathologies and tumours.

  本发明涉及苯并呋喃衍生物，能够有效激活酶复合物AMPK，适用于预防和治疗特定代谢性疾病和紊乱，如糖尿病和肥胖，免疫介导的炎症病理和肿瘤。
• Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation
  作者：Luca Antonioli、Carolina Pellegrini、Matteo Fornai、Laura Benvenuti、Vanessa D’Antongiovanni、Rocchina Colucci、Lorenzo Bertani、Clelia Di Salvo、Giorgia Semeghini、Concettina La Motta、Laura Giusti、Lorenzo Zallocco、Maurizio Ronci、Luca Quattrini、Francesco Angelucci、Vito Coviello、Won-Keun Oh、Quy Thi Kim Ha、Zoltan H. Németh、Gyorgy Haskó、Corrado Blandizzi

  DOI：10.3390/ijms22126325

  日期：——

  Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.

  Acadesine（ACA）是一种AMP-活化蛋白激酶（AMPK）的药理激活剂，在小鼠结肠炎模型中显示出有益效果，表明该药物作为管理炎症性肠病（IBDs）的替代工具。然而，ACA显示出一些药效学限制，限制了其治疗应用。我们的研究旨在评估FA-5（我们实验室合成的一种新型直接AMPK激活剂）在大鼠结肠炎实验模型中的体外和体内效果。一系列实验评估了FA5激活AMPK的能力，并在大鼠结肠炎实验模型中比较了FA5与ACA的疗效。在体外实验中，FA5诱导AMPK的磷酸化，从而激活AMPK，同时激活SIRT-1。在体内，FA5抵消了脾重增加，改善了结肠长度，改善了宏观损伤评分，并降低了DNBS处理的大鼠组织中的TNF和MDA水平。值得注意的是，与ACA相比，FA-5显示出更强的抗炎效果。这种新型AMPK激活剂FA-5显示出了改善的抗炎效果，是一种有前景的药理工具来对抗肠道炎症。