(E)-2-(3-(trifluoromethoxy)benzylidene)-2,3-dihydro-1H-inden-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (E)-2-(3-(trifluoromethoxy)benzylidene)-2,3-dihydro-1H-inden-1-one
• 英文别名: (2E)-2-[[3-(trifluoromethoxy)phenyl]methylidene]-3H-inden-1-one
• 化学式: C₁₇H₁₁F₃O₂
• 分子量: 304.268
• InChiKey: NDLVDWSSVWDQLB-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-茚酮 、 3-(三氟甲氧基)苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以47%的产率得到(E)-2-(3-(trifluoromethoxy)benzylidene)-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  设计，合成和结构与活性关系的研究含卤素的2-亚苄基-1-茚满酮衍生物，用于抑制脂多糖刺激的RAW 264.7巨噬细胞中的ROS产生。

  摘要：

  为了不断发现新的潜在抗炎药，我们系统地设计和合成了具有查耳酮结构修饰的61个2-亚苄基-1-茚满酮衍生物，并评估了其对RAW 264.7巨噬细胞中LPS刺激的ROS产生的抑制活性。 。系统的结构-活性关系研究表明，茚满酮部分的C-5，C-6或C-7位置具有羟基，苯环的邻氟，间氟或对氟，三氟甲基，三氟甲氧基和溴官能团在抑制LPS刺激的RAW 264.7巨噬细胞中ROS的产生中起重要作用。在所有测试的化合物中，6-羟基-2-（2-（三氟甲氧基）亚苄基）-2,3-二氢-1H-茚满-1-一（化合物44）对ROS产生最强的抑制活性。对作用方式的进一步研究表明，化合物44通过调节NADPH氧化酶有效抑制LPS刺激的ROS产生。这项工作的发现可能有助于设计基于2-亚苄基-茚满酮的先导化合物作为新型抗炎药。

  DOI：

  10.1016/j.ejmech.2017.03.049

文献信息

• Discovery and structure-activity relationship studies of 2-benzylidene-2,3-dihydro-1H-inden-1-one and benzofuran-3(2H)-one derivatives as a novel class of potential therapeutics for inflammatory bowel disease
  作者：Tara Man Kadayat、Suhrid Banskota、Pallavi Gurung、Ganesh Bist、Til Bahadur Thapa Magar、Aarajana Shrestha、Jung-Ae Kim、Eung-Seok Lee

  DOI：10.1016/j.ejmech.2017.06.018

  日期：2017.9

  To develop effective therapeutics for inflammatory bowel disease (IBD), 2-benzylidene-2,3-dihydro-1-Hinden-1-one and benzofuran-3(2H)-one derivatives, were designed and synthesized and their structure activity relationships (SAR) were investigated. Compounds 7, 25, 26, 32, 39, 41, 52, 54, and 55 showed potent inhibitory effect (>70%) on the TNF-alpha-induced adhesion of monocytes to colon epithelial cells, which is one of the hallmark events leading to IBD. Such inhibitory activity of the compounds correlated with their suppressive activities against the TNF-alpha-induced production of ROS; ICAM-1 and MCP-1 expression, critical molecules involved in monocyte-epithelial adhesion; and NF-kappa B transcriptional activity. In addition, compounds 41 and 55 significantly suppressed the lipopolysaccharide (LPS)-induced expression of the TNF-alpha gene, with compound 55 showing better efficacy. This inhibition of TNF-alpha expression by compounds 41 and 55 corresponded to their additional inhibitory activity against AP-1 transcriptional activity, which is another transcription factor required for high level TNF-alpha expression. The strong inhibitory activity of compound 55 against an in vivo colitis model was confirmed by its dose dependent inhibitory activity in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, demonstrating compound 55 as a new potential candidate for the development of therapeutics against IBD. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages
  作者：Aarajana Shrestha、Hye Jin Oh、Mi Jin Kim、Nirmala Tilija Pun、Til Bahadur Thapa Magar、Ganesh Bist、Hongseok Choi、Pil-Hoon Park、Eung-Seok Lee

  DOI：10.1016/j.ejmech.2017.03.049

  日期：2017.6

  inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings

  为了不断发现新的潜在抗炎药，我们系统地设计和合成了具有查耳酮结构修饰的61个2-亚苄基-1-茚满酮衍生物，并评估了其对RAW 264.7巨噬细胞中LPS刺激的ROS产生的抑制活性。 。系统的结构-活性关系研究表明，茚满酮部分的C-5，C-6或C-7位置具有羟基，苯环的邻氟，间氟或对氟，三氟甲基，三氟甲氧基和溴官能团在抑制LPS刺激的RAW 264.7巨噬细胞中ROS的产生中起重要作用。在所有测试的化合物中，6-羟基-2-（2-（三氟甲氧基）亚苄基）-2,3-二氢-1H-茚满-1-一（化合物44）对ROS产生最强的抑制活性。对作用方式的进一步研究表明，化合物44通过调节NADPH氧化酶有效抑制LPS刺激的ROS产生。这项工作的发现可能有助于设计基于2-亚苄基-茚满酮的先导化合物作为新型抗炎药。