(E)-2-(3-(4-(methylthio)benzylidene)-6-fluoro-3H-inden-1-yl)acetic acid

• 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-(3-(4-(methylthio)benzylidene)-6-fluoro-3H-inden-1-yl)acetic acid
• 英文别名: (E)-2-(5-fluoro-1-(4-(methylthio)benzylidene)-1H-inden-3-yl)acetic acid；(E)-2'-des-methyl sulindac sulfide；[6-fluoro-3-(4-methylsulfanyl-benzylidene)-3H-inden-1-yl]-acetic acid；2-Desmethylsulindac Sulfide；2-[(3E)-6-fluoro-3-[(4-methylsulfanylphenyl)methylidene]inden-1-yl]acetic acid
• 化学式: C₁₉H₁₅FO₂S
• 分子量: 326.391
• InChiKey: NEQPIGQSLNSVDO-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2-(3-(4-(methylthio)benzylidene)-6-fluoro-3H-inden-1-yl)acetic acid 以 二甲基亚砜 为溶剂， 反应 10.0h， 以10%的产率得到sulindac sulfide
  参考文献：
  名称：

  The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives

  摘要：

  Sulindac sulfide is a benzylidene-indene that is a potent, time-dependent inhibitor of cyclooxygenases-1 and -2. Removal of the 2'-methyl group from the indene ring dramatically reduces time-dependent inhibition of both enzymes but also changes the geometry of the benzylidene double bond from Z to E. Herein, we explore the importance of double bond geometry on cyclooxygenase inhibition. The Z-isomer of 2'-des-methyl sulindac sulfide was synthesized by reduction of a bromoindene precursor or by photoisomerization of the E-isomer. The Z-isomer inhibited both cyclooxygenases, but with diminished potency compared to sulindac sulfide. Thus, although the 2'-methyl group is a major determinant of time-dependent cyclooxygenase inhibition, the geometry of the benzylidene double bond plays a role as well. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.078
• 作为产物：
  描述：

  6-氟-1-茚酮 在 正丁基锂 、 sodium methylate 、 异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 11.33h， 生成 (E)-2-(3-(4-(methylthio)benzylidene)-6-fluoro-3H-inden-1-yl)acetic acid
  参考文献：
  名称：

  METHODS AND COMPOSITIONS RELATED TO A RETINOID RECEPTOR-SELECTIVE PATHWAY

  摘要：

  本文提供了与视黄醛受体选择性通路相关的方法和组合物。如本文所述，该通路可以被定向用于操纵肿瘤微环境。例如，本文描述的方法和组合物可用于诱导癌细胞凋亡。此外，包括舒林达克及其类似物在内的本文描述的组合物可用于针对该通路治疗或预防人类患者的癌症。

  公开号：

  US20150266842A1

文献信息

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

  公开号：US20050250839A1

  公开（公告）日：2005-11-10

  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.

  目前披露的主题提供了非甾体类抗炎药（NSAIDs）的衍生物，其特点是具有明显降低的环氧合酶抑制活性，但仍保留与其他多肽（如过氧化物酶体增殖物激活受体（PPARs）和γ-分泌酶）相互作用和调节活性的能力。还提供了使用这些衍生物治疗病理性疾病的方法。
• Selective oxidation of (hetero)sulfides with molecular oxygen under clean conditions
  作者：Kai-Jian Liu、Ji-Hui Deng、Jie Yang、Shao-Feng Gong、Ying-Wu Lin、Jun-Yi He、Zhong Cao、Wei-Min He

  DOI：10.1039/c9gc03713f

  日期：——

  into distinct high-value products is a particularly attractive concept and a daunting synthetic challenge. In the present work, the first example of efficient and selective oxidation of sulfides to sulfones and sulfoxides using molecular oxygen under clean conditions was established.

  为将单一原材料转化为独特的高价值产品而开发的生态友好型和可转换催化系统的开发是一个特别吸引人的概念，也是一项艰巨的合成挑战。在本工作中，建立了在清洁条件下使用分子氧将硫化物有效选择性氧化为砜和亚砜的第一个实例。
• Methods and compositions related to retinoid receptor-selective pathway
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10087156B2

  公开（公告）日：2018-10-02

  Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

  本文提供了与视黄醇受体选择性途径有关的方法和组合物。如本文所述，该通路可作为靶向来操纵肿瘤微环境。例如，本文所述的方法和组合物可用来诱导癌细胞凋亡。此外，本文所述的组合物，包括舒林酸及其类似物，可用于靶向这一途径，治疗或预防人类患者的癌症。
• Cyclooxygenase-1-Selective Inhibitors Based on the (<i>E</i>)-2′-<i>Des</i>-methyl-sulindac Sulfide Scaffold
  作者：Andy J. Liedtke、Brenda C. Crews、Cristina M. Daniel、Anna L. Blobaum、Philip J. Kingsley、Kebreab Ghebreselasie、Lawrence J. Marnett

  DOI：10.1021/jm201528b

  日期：2012.3.8

  Prostaglandins (PGs) are powerful lipid mediators in many physiological and pathophysiological responses. They are produced by oxidation of arachidonic acid (AA) by cyclo- oxygenases (COX-1 and COX-2) followed by metabolism of endoperoidde intermediates by terminal PG synthases. PG biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). Specific inhibition of COX-2 has been extensively investigated, but relatively few COX-1-selective inhibitors have been described. Recent reports of a possible contribution of COX-1 in analgesia, neuroinflammation, or carcinogenesis suggest that COX-1 is a potential therapeutic target. We designed, synthesized, and evaluated a series of (E)-2'-des-methyl-sulindac sulfide (E-DMSS) analogues for inhibition of COX-1. Several potent and selective inhibitors were discovered, and the most promising compounds were active against COX-1 in intact ovarian carcinoma cells (OVCAR-3). The compounds inhibited tumor cell proliferation but only at concentrations >100-fold higher than the concentrations that inhibit COX-1 activity. E-DMSS analogues may be useful probes of COX-1 biology in vivo and promising leads for COX-1-targeted therapeutic agents.
• METHODS AND COMPOSITIONS RELATED TO RETINOID RECEPTOR-SELECTIVE PATHWAY
  申请人：Sanford-Burnham Medical Research Institute

  公开号：US20170313668A1

  公开（公告）日：2017-11-02

  Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.