5-氯-N-[(4-氯苯基)甲基]-2-羟基苯甲酰胺 | 13156-83-7

• 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-[(4-氯苯基)甲基]-2-羟基苯甲酰胺
• 中文别名: 苯酰胺,5-氯-N-[(4-氯苯基)甲基]-2-羟基-
• 英文名称: 5-chloro-N-(4-chlorobenzyl)-2-hydroxybenzamide
• 英文别名: 5-Chloro-N-[(4-chlorophenyl)methyl]-2-hydroxybenzamide
• CAS: 13156-83-7
• 化学式: C₁₄H₁₁Cl₂NO₂
• 分子量: 296.153
• InChiKey: ZVNZJCMGSGEGKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  19
• 可旋转键数：
  3
• 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：
  2

反应信息

• 作为反应物：
  描述：

  5-氯-N-[(4-氯苯基)甲基]-2-羟基苯甲酰胺 、 氯甲酸乙酯 在 吡啶 作用下， 反应 1.0h， 以49%的产率得到6-chloro-3-(4-chlorobenzyl)-2H-1,3-benzoxazine-2,4(3H)-dione
  参考文献：
  名称：

  3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains

  摘要：

  A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.

  DOI：

  10.1016/j.farmac.2003.07.004
• 作为产物：
  描述：

  5-chloro-N-[(4-chlorophenyl)methyl]-2-methoxybenzamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以300 mg的产率得到5-氯-N-[(4-氯苯基)甲基]-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

• Structure-Activity Relationships of N-benzylsalicylamides for Inhibition of Photosynthetic Electron Transport
  作者：Katarina Kralova、Milan Perina、Karel Waisser、Josef Jampilek

  DOI：10.2174/1573406410666140815125004

  日期：2015.1.30

  Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 μmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 μmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett σ constants of the substituents on the acyl fragment (R1 = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R2 = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters π 1 and ▂of individual substituents) and electronic properties of the substituents on the acyl (σ1) and the benzylamide fragments (σ2), the contribution of σ1 being more significant than that of σ2.

  研究了61种环取代的N-苄基水杨酰胺对菠菜叶绿体中光合电子传递(PET)的抑制作用。这些化合物的抑制能力以IC50值表示，范围从2.0到425.3 μmol/L。评估的化合物中有几种可被视为有效的PET抑制剂；其中包括N-(3,4-二氯苄基)-2-羟基-5-硝基苯甲酰胺(IC50 = 2.0 μmol/L)、3,5-二溴-N-(3,4-二氯苄基)-2-羟基苯甲酰胺(IC50 = 2.3 μmol/L)和3,5-二溴-N-(4-氯苄基)-2-羟基苯甲酰胺(IC50 = 2.6 μmol/L)，这些活性与标准敌草隆(IC50 = 1.9 μmol/L)相当。PET抑制活性随着化合物亲脂性的增加以及酰基片段(R1 = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl和3,5-Br)和苄胺片段(R2 = H, 4-OCH3, 4-CH3, 4-F, 4-Cl和3,4-Cl)上取代基的Hammett σ常数之和的增加而大致线性增加。基于评估的结构-PET抑制活性关系(QSAR)证实，这些化合物的抑制活性依赖于亲脂性(log P或分布参数π1和▂)以及酰基(σ1)和苄胺片段(σ2)上取代基的电子性质，其中σ1的贡献比σ2更为显著。
• On the Relationship between the Structure and Antimycobacterial Activity of Substituted N-Benzylsalicylamides
  作者：Karel Waisser、Milan Peřina、Věra Klimešová、Jarmila Kaustová

  DOI：10.1135/cccc20031275

  日期：——

  Sixty-six N-benzylsalicylamides substituted in the acyl moiety in positions 3, 4 or 5 and in position 4 on the benzylic aromatic ring were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. To evaluate structure-antimycobacterial activity relationships (QSARs), approaches based on the Free-Wilson as well as a combination of the Free-Wilson and Hansch methods were employed (substituent constants were used to describe the influence of the benzyl substituents, indicator parameters were used for the substituents on the acyl moiety). The use of the Hammett constants for benzyl substituents was not important for QSAR equations. The quadratic representation of lipophilicity parameters (π²) was significant only in QSAR equations of antimycobacterial activity against M. avium.

  六十六种在酰基部位3、4或5以及苄芳香环上的位置4处取代的N-苄基水杨酰胺被合成。这些化合物被测试其对结核分枝杆菌、堪萨斯分枝杆菌和埃维分枝杆菌的体外抗结核活性。为了评估结构-抗结核活性关系（QSARs），采用了基于Free-Wilson方法以及Free-Wilson和Hansch方法的组合方法（取代基常数用于描述苄基取代基的影响，指示参数用于酰基部位的取代基）。对于苄基取代基，使用Hammett常数对于QSAR方程并不重要。脂溶性参数（π^2）的二次表示仅在抗结核活性对埃维分枝杆菌的QSAR方程中显著。
• [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。
• 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.
• 3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains
  作者：Karel Waisser、Milan Peřina、Jiřı́ Kuneš、Vera Klimešová、Jarmila Kaustová

  DOI：10.1016/j.farmac.2003.07.004

  日期：2003.11

  A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.