N-(4-fluorobenzyl)-2-hydroxybenzamide

• 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-(4-fluorobenzyl)-2-hydroxybenzamide
• 英文别名: N-[(4-fluorophenyl)methyl]-2-hydroxy-benzamide；N-[(4-fluorophenyl)methyl]-2-hydroxybenzamide
• 化学式: C₁₄H₁₂FNO₂
• mdl: MFCD08521802
• 分子量: 245.253
• InChiKey: WADVWWCQYOTSLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-2-hydroxybenzamide 在 sodium hydroxide 、 magnesium(II) chloride hexahydrate 作用下， 以 甲醇 、 水 为溶剂， 以45%的产率得到
  参考文献：
  名称：

  Metal-Chelating 2-Hydroxyphenyl Amide Pharmacophore for Inhibition of Influenza Virus Endonuclease

  摘要：

  The influenza virus PA endonuclease is an attractive target for development of novel anti-influenza virus therapeutics. Reported PA inhibitors chelate the divalent metal ion(s) in the enzyme's catalytic site, which is located in the N-terminal part of PA (PA-Nter). In this work, a series of 2-hydroxybenzamide-based compounds have been synthesized and biologically evaluated in order to identify the essential pharmacophoric motif, which could be involved in functional sequestration of the metal ions (probably Mg2+) in the catalytic site of PA. By using HL1, H2L2, and HL3 as Model ligands with Mg2+ ions, we isolated and fully characterized a series of complexes and tested them for inhibitory activity toward PA-Nter endonuclease. H2L2 and the corresponding Mg2+ complex showed an. interesting inhibition of the endonuclease activity. The crystal structures of the uncomplexed HL1 and H2L2 and of the isolated magnesium complex [Mg(L-3)(2)(MeOH)(2)] 2MeOH were solved by X-ray diffraction analysis. Furthermore, the speciation models for HL1, H2L2, and HL3 with Mg2+ were obtained, and the formation constants of the complexes were measured. Preliminary docking calculations were conducted to-investigate the interactions of the title compounds with essential amino acids in the PA-Nter active site. These findings supported the "two-metal" coordination of divalent ions by a donor triad atoms chemotype as a powerful strategy to develop more potent PA endonuclease inhibitors.

  DOI：

  10.1021/mp400482a
• 作为产物：
  描述：

  N-(4-氟苄基)-2-甲氧基苯甲酰胺 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-(4-fluorobenzyl)-2-hydroxybenzamide
  参考文献：
  名称：

  Metal-chelating properties and antiviral activity of some 2-hydroxyphenyl amides

  摘要：

  Influenza virus is an hot topic in medicinal chemistry and great efforts are ongoing for the discover of new antivirals able to overcome problems related to resistant strains and adverse side effects of current drugs. Influenza virus endonuclease is an attractive target for antiviral drug development and in particular the strategy to chelate the metal ion(s) within the active site proved to be an efficient mode to inhibit enzymatic activity. Our previous findings revealed that 2-hydroxyamide derivatives are able to chelate Mg2+ ions, forming complexes with different stoichiometric ratios. Here we report on the activity of the three ligands N-(4-fluorobenzy1)-2-hydroxybenzamide, N-(4-fluorobenzyl)-2,3-dihydroxybenzamide, and N1, N3-bis(4-fluorobenzyI)-2-hydroxyisophthalamide, containing the salicylic group, and their Mg2+ complexes (7)-(9), evaluated by means of virus yield assay in influenza virus-infected MDCK cells and vRNP reconstitution assay in HEK293T cells. In some cases, promising anti-influenza activities with EC50 values in the low micromolar range were found. As a contribute to clarify the activity in cells of the ligands, here we also present a study on the their coordinating properties towards the other essential metal ion Cu(II), carried out by potentiometric and calorimetric measurements. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2017.03.032

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。
• <i>N-</i>Benzylsalicylthioamides: Highly Active Potential Antituberculotics
  作者：Rafael Doležal、Karel Waisser、Eva Petrlíková、Jirí Kuneš、Lenka Kubicová、Miloš Machácek、Jarmila Kaustová、Hans Martin Dahse

  DOI：10.1002/ardp.200800032

  日期：2009.2

  electron donating effect of the substituents in the acyl moiety and decreased with the electrophilic superdelocalizability of the molecules. The most active compounds are more active than isoniazid (INH) and are active against INH‐resistant potential pathogenic strains of mycobacterium.

  合成了 29 种新的 N-苄基水杨基硫代酰胺衍生物，并测试了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的体外抗分枝杆菌活性。通过定量构效关系（QSAR）分析活性。活性随着酰基部分中取代基的亲脂性和给电子效应的增加而增加，并随着分子的亲电超离域性而降低。最活跃的化合物比异烟肼 (INH) 更具活性，并且对 INH 耐药的潜在分枝杆菌致病菌株具有活性。
• HIV INTEGRASE INHIBITORS
  申请人：National Institutes of Health

  公开号：US20140142137A1

  公开（公告）日：2014-05-22

  Provided herein, inter alia, are novel compounds for the inhibition of HIV integrase. The compounds disclosed herein are useful for methods of treating HIV infection in a subject in need thereof.

  本文提供了一些新的化合物，用于抑制HIV整合酶。本文所披露的化合物可用于治疗需要治疗HIV感染的人体内的方法。
• [EN] HIV INTEGRASE INHIBITORS<br/>[FR] INHIBITEURS DE L'INTÉGRASE DU VIH
  申请人：UNIV CALIFORNIA

  公开号：WO2012106534A3

  公开（公告）日：2012-11-15
• 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.