(E)-2-(1-(4-ethynylbenzylidene)-5-fluoro-1H-inden-3-yl)ethanoic acid | 1049800-37-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: (E)-2-(1-(4-ethynylbenzylidene)-5-fluoro-1H-inden-3-yl)ethanoic acid
• 英文别名: (E)-2-(1-(4-Ethynylbenzylidene)-5-fluoro-1H-inden-3-yl)ethanoicacid；2-[(3E)-3-[(4-ethynylphenyl)methylidene]-6-fluoroinden-1-yl]acetic acid
• CAS: 1049800-37-4
• 化学式: C₂₀H₁₃FO₂
• 分子量: 304.32
• InChiKey: OLMBCUZWJVTVBA-OQLLNIDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 2-(5-fluoro-1H-inden-3-yl)acetate 、 4-乙炔基苯甲醛 在 sodium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 生成 (E)-2-(1-(4-ethynylbenzylidene)-5-fluoro-1H-inden-3-yl)ethanoic acid
  参考文献：
  名称：

  Sulindac Derivatives That Activate the Peroxisome Proliferator-activated Receptor γ but Lack Cyclooxygenase Inhibition

  摘要：

  A series of novel derivatives of the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide were synthesized as potential agonists of the peroxisome proliferator-activated receptor gamma (PPAR gamma). Nonpolar and aromatic substitutions oil the benzylidene ring as well as retention of the carboxylic acid side chain were required for optimal activity. Compound 24 was as potent a compound as my other in the series with,in EC(50) Of 0-1 mu M for the induction of peroxisome proliferator response element (PPRE)-luciferase activity. Direct binding of compound 24 to PPAR gamma was demonstrated by the displacement of I. 3 H]troglitazone, a PPAR gamma agonist, in a scintillation proximity assay. Compound 24 also stimulated the binding of PPAR gamma to a PPRE-containing oligonucleotide and induced expression of liver fatty-acid binding protein (L-FABP) and adipocyte fatty acid-binding protein (aP2), two established PPAR gamma target genes. Taken together, these compounds represent potential leads in the development of novel PPAR gamma agonists.

  DOI：

  10.1021/jm700969c

文献信息

• Indoleacetic acid and indenacetic acid derivatives as therapeutic agents with reduced gastrointestinal toxicity
  申请人：Marnett Lawrence J.

  公开号：US20090118290A1

  公开（公告）日：2009-05-07

  The presently disclosed subject matter provides derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) that are characterized by substantially reduced cyclooxygenase inhibiting activity, yet retain the ability to interact with and modulate the activities of other polypeptides such as the class of peroxisome proliferators-activated receptors (PPARs) and γ-secretase. Also provided are methods of using the derivatives to treat pathological disorders.

  目前公开的主题提供了非甾体类抗炎药（NSAIDs）的衍生物，其特征是具有显著降低的环氧合酶抑制活性，但仍保留与其他多肽相互作用和调节活性的能力，如过氧化物酶体增殖物激活受体（PPARs）和γ-分泌酶。还提供了使用这些衍生物治疗病理性疾病的方法。
• US8168656B2
  申请人：——

  公开号：US8168656B2

  公开（公告）日：2012-05-01
• Sulindac Derivatives That Activate the Peroxisome Proliferator-activated Receptor γ but Lack Cyclooxygenase Inhibition
  作者：Andrew S. Felts、Brianna S. Siegel、Shiu M. Young、Christopher W. Moth、Terry P. Lybrand、Andrew J. Dannenberg、Lawrence J. Marnett、Kotha Subbaramaiah

  DOI：10.1021/jm700969c

  日期：2008.8.1

  A series of novel derivatives of the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide were synthesized as potential agonists of the peroxisome proliferator-activated receptor gamma (PPAR gamma). Nonpolar and aromatic substitutions oil the benzylidene ring as well as retention of the carboxylic acid side chain were required for optimal activity. Compound 24 was as potent a compound as my other in the series with,in EC(50) Of 0-1 mu M for the induction of peroxisome proliferator response element (PPRE)-luciferase activity. Direct binding of compound 24 to PPAR gamma was demonstrated by the displacement of I. 3 H]troglitazone, a PPAR gamma agonist, in a scintillation proximity assay. Compound 24 also stimulated the binding of PPAR gamma to a PPRE-containing oligonucleotide and induced expression of liver fatty-acid binding protein (L-FABP) and adipocyte fatty acid-binding protein (aP2), two established PPAR gamma target genes. Taken together, these compounds represent potential leads in the development of novel PPAR gamma agonists.