5-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)-2-hydroxybenzamide | 934192-70-8

• 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: 5-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)-2-hydroxybenzamide
• 英文别名: 5-chloro-N-[2-chloro-4-(trifluoromethyl)phenyl]-2-hydroxy-benzamide；5-chloro-N-[2-chloro-4-(trifluoromethyl)phenyl]-2-hydroxybenzamide
• CAS: 934192-70-8
• 化学式: C₁₄H₈Cl₂F₃NO₂
• 分子量: 350.124
• InChiKey: HWSURKONPGIXBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氯代水杨酸 、 5-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)-2-hydroxybenzamide 在 吡啶 、 三氯化磷 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以31%的产率得到N-[4-Bromo-2-(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide
  参考文献：
  名称：

  Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2012.10.056
• 作为产物：
  描述：

  5-chloro-N-[2-chloro-4-(trifluoromethyl)phenyl]-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-chloro-N-(2-chloro-4-(trifluoromethyl)phenyl)-2-hydroxybenzamide
  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。
• COMPOUNDS AND METHODS FOR INHIBITING VIRAL REPLICATION AND METHODS OF TREATING AND PREVENTING FLAVIVIRAL INFECTIONS
  申请人：Health Research, Inc.

  公开号：US20220024884A1

  公开（公告）日：2022-01-27

  The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The present disclosure further relates to methods of inhibiting viral replication including contacting one or more cells that have been infected with a virus with an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the virus comprises a flavivirus. Also disclosed is a method of treating and/or preventing a flavivirus infection and/or a condition resulting from a flavivirus infection including administering an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof under conditions effective to treat and/or prevent a flavivirus infection and/or a condition resulting from a flavivirus infection.

  本公开涉及公式（I）的化合物或其药用可接受盐。本公开进一步涉及抑制病毒复制的方法，包括将感染病毒的一个或多个细胞与公式（I）的化合物或其药用可接受盐的有效量接触，其中该病毒包括黄病毒。还公开了一种治疗和/或预防黄病毒感染和/或由黄病毒感染引起的病况的方法，包括在有效条件下给予公式（I）的化合物或其药用可接受盐的有效量，以治疗和/或预防黄病毒感染和/或由黄病毒感染引起的病况。
• [EN] NOVEL MITOCHONDRIAL UNCOUPLERS FOR TREATMENT OF METABOLIC DISEASES AND CANCER<br/>[FR] NOUVEAUX DÉCOUPLANTS MITOCHONDRIAUX POUR LE TRAITEMENT DE MALADIES MÉTABOLIQUES ET DU CANCER
  申请人：JIN SHENGKAN

  公开号：WO2017201313A1

  公开（公告）日：2017-11-23

  The present disclosure relates to benzamide compounds, prodrugs of the compounds, pharmaceutical compositions containing the compounds and/or the prodrugs and methods of using the compounds, prodrugs and pharmaceutical compositions in the treatment of diseases related to lipid metabolism including diabetes, Non-Alcholic Fatty Liver Disease (NAFLD), Non-Alcholic Steathohepatitis (NASH), diseases caused by abnormal cell proliferation including cancer, psoriasis, and infectious diseases.

  本公开涉及苯甲酰胺化合物、该化合物的前体药物、含有该化合物和/或前体药物的药物组合物，以及使用这些化合物、前体药物和药物组合物治疗与脂质代谢相关的疾病，包括糖尿病、非酒精性脂肪肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、由异常细胞增殖引起的疾病，包括癌症、牛皮癣和传染病的方法。
• Structure–activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure
  作者：Robert A. Mook、Jiangbo Wang、Xiu-Rong Ren、Minyong Chen、Ivan Spasojevic、Larry S. Barak、H. Kim Lyerly、Wei Chen

  DOI：10.1016/j.bmc.2015.07.001

  日期：2015.9

  Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide’s low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly

  Wnt信号通路在器官发育和组织稳态的调节中发挥着关键作用。Wnt 活性失调是导致包括癌症在内的许多疾病的主要潜在机制之一。我们之前报道过 FDA 批准的驱虫药 Niclosamide 可抑制 Wnt/β-catenin 信号传导，并在体外和体内抑制结肠癌细胞的生长。Niclosamide 是一种多功能药物，除了抑制 Wnt/β-catenin 信号传导外，还具有重要的生物活性。在这里，我们研究了氯硝柳胺的苯胺和水杨酰胺区域中 Wnt 信号传导抑制的 SAR。我们发现4'-硝基取代基可以有效地被三氟甲基或氯取代，并且抑制效力取决于苯胺环中的取代模式。非苯胺、N-甲基酰胺和反向酰胺衍生物失去了显着的效力，而酰化水杨酰胺衍生物抑制信号传导的效力与非酰基衍生物相似。口服氯硝柳胺的全身暴露量较低，可能会阻碍其用于治疗全身性疾病。为了克服这一限制，我们鉴定了氯硝柳胺的酰基衍生物 DK-520（化合物3
• Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection
  作者：Khalida Shamim、Miao Xu、Xin Hu、Emily M Lee、Xiao Lu、Ruili Huang、Pranav Shah、Xin Xu、Catherine Z. Chen、Min Shen、Hui Guo、Lu Chen、Zina Itkin、Richard T. Eastman、Paul Shinn、Carleen Klumpp-Thomas、Sam Michael、Anton Simeonov、Donald C. Lo、Guo-li Ming、Hongjun Song、Hengli Tang、Wei Zheng、Wenwei Huang

  DOI：10.1016/j.bmcl.2021.127906

  日期：2021.5

  focusing on the anilide and salicylic acid regions of niclosamide to improve physicochemical properties such as microsomal metabolic stability, permeability and solubility. We found that the 5-bromo substitution in the salicylic acid region retains potency while providing better drug-like properties. Other modifications in the anilide region with 2′-OMe and 2′-H substitutions were also advantageous

  寨卡病毒已成为全球人类健康的潜在威胁。之前的药物再利用筛选确定已批准的驱虫药氯硝柳胺是寨卡病毒感染的小分子抑制剂。然而，由于抗蠕虫药物通常设计为口服时吸收率较低，氯硝柳胺非常有限的生物利用度可能会阻碍其直接重新用作抗病毒药物。在这里，我们针对氯硝柳胺的苯胺和水杨酸区域进行了 SAR 研究，以改善微粒体代谢稳定性、渗透性和溶解性等理化性质。我们发现水杨酸区域的 5-溴取代保留了效力，同时提供了更好的药物样特性。具有 2'-OMe 和 2'-H 取代的苯胺区域的其他修饰也是有利的。我们发现4'-NO 2取代基可以被4'-CN或4'-CF 3取代基取代。总之，这些修饰为优化氯硝柳胺的结构提供了基础，以改善氯硝柳胺类似物作为治疗寨卡和其他病毒感染的药物先导候选药物的全身暴露。事实上，关键的类似物也能够将细胞从 SARS-CoV-2 感染的细胞病变效应中拯救出来，这表明与针对 COVID-19 大流行的治疗策略的相关性。