5-氯-N-(2-氟-4-硝基苯基)-2-羟基苯甲酰胺 | 1008121-11-6

• 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-(2-氟-4-硝基苯基)-2-羟基苯甲酰胺
• 英文名称: 5-chloro-N-(2-fluoro-4-nitrophenyl)-2-hydroxybenzamide
• CAS: 1008121-11-6
• 化学式: C₁₃H₈ClFN₂O₄
• 分子量: 310.669
• InChiKey: GYJUECWQOUADHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 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：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氯-N-(2-氟-4-硝基苯基)-2-羟基苯甲酰胺 在 氯化铵 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 水 为溶剂， 反应 28.5h， 生成 5-chloro-N-(4-(cyclopentylamino)-2-fluorophenyl)-2-hydroxybenzamide
  参考文献：
  名称：

  新型取代的N-（4-氨基-2-氯苯基）-5-氯-2-羟基苯甲酰胺类似物作为有效的人腺病毒抑制剂的发现

  摘要：

  在免疫功能低下的患者和社区获得性肺炎的健康个体中，有效治疗人腺病毒（HAdV）的方法仍未满足医疗需求。我们在本文中报道了一系列新颖的取代的N-（4-氨基-2-氯苯基）-5-氯-2-羟基苯甲酰胺类似物作为有效的HAdV抑制剂。化合物6，15，29，40，43，46，47，和54个显示出增加的选择性指数（SI> 100）相比，铅化合物氯硝柳胺，同时保持亚微摩尔到针对的HAdV低微摩尔效力。初步的机理研究表明，化合物6化合物46和47可能抑制HAdV生命周期的后续步骤，而43和43可能靶向HAdV DNA复制过程。值得注意的是，在这些衍生物中，化合物15的抗HAdV活性提高（IC 50 = 0.27μM），细胞毒性显着降低（CC 50 = 156.8μM），体内毒性低（仓鼠最大耐受剂量= 150 mg / kg）与尼克洛沙胺相比，支持其进一步治疗HAdV感染的体内功效研究。

  DOI：

  10.1021/acs.jmedchem.0c01226
• 作为产物：
  描述：

  5-chloro-N-(2-fluoro-4-nitrophenyl)-2-methoxybenzamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以318 mg的产率得到5-氯-N-(2-氟-4-硝基苯基)-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

• [EN] SALICYLAMIDE DERIVATIVES AND RELATED METHODS OF MAKING<br/>[FR] DÉRIVÉS DE SALICYLAMIDE ET MÉTHODES DE FABRICATION ASSOCIÉES
  申请人：UNIV TEXAS

  公开号：WO2021151104A1

  公开（公告）日：2021-07-29

  Certain embodiments describe antiviral compounds and related methods of using such compounds.

  某些实施例描述了抗病毒化合物及其使用方法。
• 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
• Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer
  作者：Borui Kang、Madhusoodanan Mottamal、Qiu Zhong、Melyssa Bratton、Changde Zhang、Shanchun Guo、Ahamed Hossain、Peng Ma、Qiang Zhang、Guangdi Wang、Florastina Payton-Stewart

  DOI：10.3390/ph16050735

  日期：——

  Niclosamide effectively downregulates androgen receptor variants (AR-Vs) for treating enzalutamide and abiraterone-resistant prostate cancer. However, the poor pharmaceutical properties of niclosamide due to its solubility and metabolic instability have limited its clinical utility as a systemic treatment for cancer. A novel series of niclosamide analogs was prepared to systematically explore the structure–activity relationship and identify active AR-Vs inhibitors with improved pharmaceutical properties based on the backbone chemical structure of niclosamide. Compounds were characterized using 1H NMR, 13C NMR, MS, and elemental analysis. The synthesized compounds were evaluated for antiproliferative activity and downregulation of AR and AR-V7 in two enzalutamide-resistant cell lines, LNCaP95 and 22RV1. Several of the niclosamide analogs exhibited equivalent or improved anti-proliferation effects in LNCaP95 and 22RV1 cell lines (B9, IC50 LNCaP95 and 22RV1 = 0.130 and 0.0997 μM, respectively), potent AR-V7 down-regulating activity, and improved metabolic stability. In addition, both a traditional structure–activity relationship (SAR) and 3D-QSAR analysis were performed to guide further structural optimization. The presence of two -CF3 groups of the most active B9 in the sterically favorable field and the presence of the -CN group of the least active B7 in the sterically unfavorable field seem to make B9 more potent than B7 in the antiproliferative activity.

  尼可刹米能有效下调雄激素受体变体（AR-Vs），用于治疗恩杂鲁胺和阿比特龙耐药的前列腺癌。然而，由于尼可刹米的溶解性和代谢不稳定性，其药物特性较差，限制了其作为全身性癌症治疗药物的临床应用。本研究制备了一系列新型尼可刹米类似物，以系统地探索其结构-活性关系，并在尼可刹米骨架化学结构的基础上鉴定出具有更好药物特性的活性 AR-Vs 抑制剂。利用 1H NMR、13C NMR、MS 和元素分析对化合物进行了表征。对合成的化合物进行了评估，以确定其在两种耐恩扎鲁胺细胞系（LNCaP95 和 22RV1）中的抗增殖活性以及对 AR 和 AR-V7 的下调作用。几种烟酰胺类似物在 LNCaP95 和 22RV1 细胞系中表现出了同等或更好的抗增殖效果（B9，IC50 LNCaP95 和 22RV1 分别为 0.130 和 0.0997 μM）、强效的 AR-V7 下调活性以及更好的代谢稳定性。此外，还进行了传统的结构-活性关系（SAR）和三维-QSAR 分析，以指导进一步的结构优化。活性最高的 B9 的两个 -CF3 基团位于立体有利区域，而活性最低的 B7 的 -CN 基团位于立体不利区域，这似乎使 B9 的抗增殖活性比 B7 更强。
• Methods and compositions for treating conditions associated with an abnormal inflammatory responses
  申请人：First Wave Bio, Inc.

  公开号：US10292951B2

  公开（公告）日：2019-05-21

  This disclosure features chemical entities (e.g., a compound exhibiting activity as a mitochondrial uncoupling agent or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as niclosamide or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as a niclosamide analog, or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof) that are useful, e.g., for treating one or more symptoms of a pathology characterized by an abnormal inflammatory response (e.g., inflammatory bowel diseases) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

  本公开的化学实体（例如，具有线粒体解偶联剂活性的化合物或其药学上可接受的盐和/或水合物和/或共晶体；例如，化合物，如烟酰胺或其药学上可接受的盐和/或水合物和/或共晶体；例如、化合物，如尼可刹米类似物，或其药学上可接受的盐和/或水合物和/或共晶体），这些化合物可用于治疗受试者（如人类）中以异常炎症反应（如炎症性肠病）为特征的病理学的一种或多种症状。本公开内容还包括组合物以及使用和制造组合物的其他方法。
• Methods and compositions for treating conditions associated with an abnormal inflammatory response
  申请人：First Wave Bio, Inc.

  公开号：US10772854B2

  公开（公告）日：2020-09-15

  This disclosure features chemical entities (e.g., a compound exhibiting activity as a mitochondrial uncoupling agent or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as niclosamide or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof; e.g., a compound, such as a niclosamide analog, or a pharmaceutically acceptable salt and/or hydrate and/or cocrystal thereof) that are useful, e.g., for treating one or more symptoms of a pathology characterized by an abnormal inflammatory response (e.g., inflammatory bowel diseases) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

  本公开的化学实体（例如，具有线粒体解偶联剂活性的化合物或其药学上可接受的盐和/或水合物和/或共晶体；例如，化合物，如烟酰胺或其药学上可接受的盐和/或水合物和/或共晶体；例如、化合物，如尼可刹米类似物，或其药学上可接受的盐和/或水合物和/或共晶体），这些化合物可用于治疗受试者（如人类）中以异常炎症反应（如炎症性肠病）为特征的病理学的一种或多种症状。本公开内容还包括组合物以及使用和制造组合物的其他方法。