2-((3-chloro-2-(2,3-dihydrobenzofuran-5-yl)phenyl)amino)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((3-chloro-2-(2,3-dihydrobenzofuran-5-yl)phenyl)amino)benzoic acid
• 英文别名: 2-[[3-Chloranyl-2-(2,3-dihydro-1-benzofuran-5-yl)phenyl]amino]benzoic acid；2-[3-chloro-2-(2,3-dihydro-1-benzofuran-5-yl)anilino]benzoic acid
• 化学式: C₂₁H₁₆ClNO₃
• 分子量: 365.816
• InChiKey: LOEBSRSQBHSNFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-二氯硝基苯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 铁粉 、 potassium carbonate 、 氯化铵 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 甲苯 为溶剂， 反应 22.42h， 生成 2-((3-chloro-2-(2,3-dihydrobenzofuran-5-yl)phenyl)amino)benzoic acid
  参考文献：
  名称：

  Exploration of Fragment Binding Poses Leading to Efficient Discovery of Highly Potent and Orally Effective Inhibitors of FABP4 for Anti-inflammation

  摘要：

  Fatty-acid binding protein 4 (FABP4) is a promising therapeutic target for immunometabolic diseases, while its potential for systemic inflammatory response syndrome treatment has not been explored. Here, a series of 2-(phenylamino)benzoic acids as novel and potent FABP4 inhibitors are rationally designed based on an interesting fragment that adopts multiple binding poses within FABP4. A fusion of these binding poses leads to the design of compound 3 with an similar to 460-fold improvement in binding affinity compared to the initial fragment. A subsequent structure-aided optimization upon 3 results in a promising lead (17) with the highest binding affinity among all the inhibitors, exerting a significant anti-inflammatory effect in cells and effectively attenuating a systemic inflammatory damage in mice. Our work therefore presents a good example of lead compound discovery derived from the multiple binding poses of a fragment and provides a candidate for development of drugs against inflammation-related diseases.

  DOI：

  10.1021/acs.jmedchem.9b02107

文献信息

• 2-芳基胺类化合物及其制备方法和应用
  申请人：中国科学院上海药物研究所

  公开号：CN112745237B

  公开（公告）日：2023-06-20

  本发明公开了一种2‑芳基胺类化合物及其制备方法和应用，2‑芳基胺类化合物结构如式I所示，式中，各取代基的定义如说明书和权利要求书中所述。本发明的化合物对脂肪酸结合蛋白4具有良好的抑制效果，可以用于预防、治疗或辅助治疗与FABP4活性或表达相关的代谢性疾病、炎症和癌症。
• Exploration of Fragment Binding Poses Leading to Efficient Discovery of Highly Potent and Orally Effective Inhibitors of FABP4 for Anti-inflammation
  作者：Haixia Su、Yi Zou、Guofeng Chen、Huixia Dou、Hang Xie、Xiaojing Yuan、Xianglei Zhang、Naixia Zhang、Minjun Li、Yechun Xu

  DOI：10.1021/acs.jmedchem.9b02107

  日期：2020.4.23

  Fatty-acid binding protein 4 (FABP4) is a promising therapeutic target for immunometabolic diseases, while its potential for systemic inflammatory response syndrome treatment has not been explored. Here, a series of 2-(phenylamino)benzoic acids as novel and potent FABP4 inhibitors are rationally designed based on an interesting fragment that adopts multiple binding poses within FABP4. A fusion of these binding poses leads to the design of compound 3 with an similar to 460-fold improvement in binding affinity compared to the initial fragment. A subsequent structure-aided optimization upon 3 results in a promising lead (17) with the highest binding affinity among all the inhibitors, exerting a significant anti-inflammatory effect in cells and effectively attenuating a systemic inflammatory damage in mice. Our work therefore presents a good example of lead compound discovery derived from the multiple binding poses of a fragment and provides a candidate for development of drugs against inflammation-related diseases.