5-氯-N-(3,4-二氟苯基)-2-羟基苯甲酰胺 | 634186-48-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-氯-N-(3,4-二氟苯基)-2-羟基苯甲酰胺
• 英文名称: 5-chloro-N-(3,4-difluorophenyl)-2-hydroxybenzamide
• CAS: 634186-48-4
• 化学式: C₁₃H₈ClF₂NO₂
• 分子量: 283.662
• InChiKey: AKJGOFWBCZWMCU-UHFFFAOYSA-N

物化性质

• 沸点：
  330.2±42.0 °C(Predicted)
• 密度：
  1.516±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-chloro-N-(3,4-difluorophenyl)-2-methoxybenzamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以120 mg的产率得到5-氯-N-(3,4-二氟苯基)-2-羟基苯甲酰胺
  参考文献：
  名称：

  Structure–Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection

  摘要：

  The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.

  DOI：

  10.1021/acs.jmedchem.9b01950

文献信息

• Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistant S. aureus
  作者：Jhajan Lal、Grace Kaul、Abdul Akhir、Shabina B. Ansari、Sidharth Chopra、Damodara N. Reddy

  DOI：10.1007/s00044-021-02808-4

  日期：2021.12

  vancomycin-resistant Staphylococcus aureus (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited S. aureus

  耐甲氧西林金黄色葡萄球菌(MRSA) 和耐万古霉素金黄色葡萄球菌(VRSA) 是全球皮肤和软组织感染的主要原因。为解决由于多重耐药 (MDR) 细菌感染引起的紧急情况，合成了一系列新型氟和三氟甲基取代的水杨酰苯胺衍生物，并对其抗菌活性进行了研究。MIC 数据显示，这些化合物特异性抑制金黄色葡萄球菌（MIC 0.25–64 µg/mL）。MIC < 1 µg/mL的化合物对 Vero 细胞的体外细胞毒性导致鉴定出四种化合物（20、22、24和25 ）)，选择性指数高于 10。这四种化合物针对 MDR S. aureus小组进行了测试。值得注意的是，5-氯-N- (4'-溴-3'-三氟甲基苯基)-2-羟基苯甲酰胺 ( 22 ) 对 9 种 MRSA 和 3 种 VRSA 菌株表现出优异的活性，MIC 为 0.031–0.062 µg/mL，显着优于对照药物甲氧西林和万古霉素。比较时间-杀灭动力
• 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.
• Structure–Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection
  作者：Jimin Xu、Judith Berastegui-Cabrera、Haiying Chen、Jerónimo Pachón、Jia Zhou、Javier Sánchez-Céspedes

  DOI：10.1021/acs.jmedchem.9b01950

  日期：2020.3.26

  The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.