N-(5-chloro-2-hydroxyphenyl)-3,5-bis(trifluoromethyl)benzamide | 1417658-07-1

• 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: N-(5-chloro-2-hydroxyphenyl)-3,5-bis(trifluoromethyl)benzamide
• 英文别名: N-(5-chloro-2-hydroxy-phenyl)-3,5-bis(trifluoromethyl)benzamide
• CAS: 1417658-07-1
• 化学式: C₁₅H₈ClF₆NO₂
• 分子量: 383.677
• InChiKey: XFKHDOHWIMSKRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(2-hydroxyphenyl)-3,5-bistrifluoromethylbenzamide 在 iron(III) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以86%的产率得到N-(5-chloro-2-hydroxyphenyl)-3,5-bis(trifluoromethyl)benzamide
  参考文献：
  名称：

  使用氨基导向基团的铁 (III) 介导的酚类亲核卤化

  摘要：

  在 Fe(III) 试剂的存在下，实现了富电子氨基酚的酰胺定向区域选择性和亲核卤化反应。卤化物可以依次引入特定位置以形成单卤代、二卤代和混合二卤代氨基酚，主要以一锅法的方式进行。

  DOI：

  10.1002/ejoc.202200387

文献信息

• 4-氯-2-酰氨基酚的合成方法
  申请人：西北农林科技大学

  公开号：CN114380709B

  公开（公告）日：2023-07-21

  本发明涉及一种4‑氯‑2‑酰氨基酚的合成方法，2‑氨基酚与酰氯反应，生成2‑酰氨基酚类化合物；化合物与三个当量的三氯化铁在二氯甲烷加热条件回流下反应得到4‑氯‑2‑酰氨基酚类化合物。本发明合成原料易得，实验条件温和，避免了使用价格昂贵和高毒性的原料，操作安全，对环境污染小，收率较高，且可为IKKβ的一种选择性抑制剂IMD‑0354及中枢肌肉松弛剂氯唑沙宗(Chlorzoxazone)的合成提供新的方法。
• Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling
  作者：Ill-Young Lee、Todd D. Gruber、Amanda Samuels、Minhan Yun、Bora Nam、Minseo Kang、Kathryn Crowley、Benjamin Winterroth、Helena I. Boshoff、Clifton E. Barry

  DOI：10.1016/j.bmc.2012.10.056

  日期：2013.1

  A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics. Published by Elsevier Ltd.
• Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists
  作者：Maoqun Tian、Aliaa Abdelrahman、Younis Baqi、Eduardo Fuentes、Djamil Azazna、Claudia Spanier、Sabrina Densborn、Sonja Hinz、Ralf Schmid、Christa E. Müller

  DOI：10.1021/acs.jmedchem.0c00435

  日期：2020.6.11

  Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (1, IC50 0.0192 mu M) and N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide (14, IC50 0.0231 mu M), displayed >500-fold selectivity versus P2X2 and P2X3, and 10-fold selectivity versus P2X4 and P2X7 receptors, and inhibited collagen-induced platelet aggregation. They behaved as negative allosteric modulators, and molecular modeling studies suggested an extracellular binding site. Besides selective P2X1 antagonists, compounds with ancillary P2X4 and/or P2X7 receptor inhibition were discovered. These compounds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.
• Iron(III)‐Mediated Nucleophilic Halogenation of Phenols Using an Amido Directing Group
  作者：Ye Yuan、Dou Guo、Yibo Liu、Congcong Wan、Dongbiao Lu、Hongxiang Yang、Yufan Lu、Wei Meng、Hongling Wang、Xiang Zhang

  DOI：10.1002/ejoc.202200387

  日期：2022.5.6

  An amido-directing regioselective and nucleophilic halogenation reaction of electron-rich amidophenols was realized in the presence of Fe(III) reagents. Halides could be sequentially introduced to specific positions to form mono-, di- and mixed di- halogenated amidophenols mostly in one-pot manner.

  在 Fe(III) 试剂的存在下，实现了富电子氨基酚的酰胺定向区域选择性和亲核卤化反应。卤化物可以依次引入特定位置以形成单卤代、二卤代和混合二卤代氨基酚，主要以一锅法的方式进行。