3,5-dichloro-2-hydroxy-benzoic acid p-anisidide | 54850-01-0

• 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: 3,5-dichloro-2-hydroxy-benzoic acid p-anisidide
• 英文别名: 3,5-Dichlor-2-hydroxy-benzoesaeure-p-anisidid；3,5-dichloro-2-hydroxy-N-(4-methoxyphenyl)benzamide
• CAS: 54850-01-0
• 化学式: C₁₄H₁₁Cl₂NO₃
• 分子量: 312.152
• InChiKey: WPOAGRRIROBDFF-UHFFFAOYSA-N

物化性质

• 熔点：
  173-174 °C
• 沸点：
  394.6±42.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 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：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-dichloro-2-hydroxy-benzoic acid p-anisidide 、 氯甲酸乙酯 以 吡啶 为溶剂， 反应 1.0h， 以72%的产率得到6,8-Dichloro-3-(4-methoxyphenyl)-1,3-benzoxazine-2,4-dione
  参考文献：
  名称：

  抗分枝杆菌物质的化学结构与其对非典型菌株的活性之间的关系。第 14 部分：3-Aryl-6,8-dihalo-2H-1,3-benzoxazine-2,4 (3H) -diones

  摘要：

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估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抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。

  DOI：

  10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2
• 作为产物：
  描述：

  3,5-二溴-2-羟基苯甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 3,5-dichloro-2-hydroxy-benzoic acid p-anisidide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activities of Closantel Analogues: Structural Promiscuity and Its Impact on Onchocerca volvulus

  摘要：

  Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.

  DOI：

  10.1021/jm200364n

文献信息

• Substituted Salicylanilides as Inhibitors of Two-Component Regulatory Systems in Bacteria
  作者：Mark J. Macielag、James P. Demers、Stephanie A. Fraga-Spano、Dennis J. Hlasta、Sigmond G. Johnson、Ramesh M. Kanojia、Ronald K. Russell、Zhihua Sui、Michele A. Weidner-Wells、Harvey Werblood、Barbara D. Foleno、Raul M. Goldschmidt、Michael J. Loeloff、Glenda C. Webb、John F. Barrett

  DOI：10.1021/jm9803572

  日期：1998.7.1

  A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron-attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity.

  基于水杨酰苯胺的筛选命中氯梭菌（1）和四氯水杨酰苯胺（9），发现了一种新型的细菌两组分调节系统（TCS）抑制剂。系统的SAR研究与模型TCS KinA / Spo0F相比，证明了水杨酰环中吸引电子的取代基和苯胺部分中的疏水基团具有最佳活性的重要性。另外，含有2，3-二羟基苯甲腈结构基序的衍生物8和16是KinA激酶自磷酸化的有效抑制剂，IC50分别为2.8和6. 3 µM。化合物8还以低于抑制生长的浓度抑制了基因工程化粪肠球菌细胞系中介导万古霉素抗性的TCS（VanS / VanR）。氯沙坦（1），四氯水杨基苯胺（9），
• Ioffe; Sal'manowitsch, Zhurnal Obshchei Khimii, 1959, vol. 29, p. 2685,2688; engl. Ausg. S. 2652, 2654
  作者：Ioffe、Sal'manowitsch

  DOI：——

  日期：——
• Relationships Between the Chemical Structure of Antimycobacterial Substances and Their Activity Against Atypical Strains. Part 14: 3-Aryl-6,8-dihalogeno-2H-1,3-benzoxazine-2,4(3H)-diones
  作者：Karel Waisser、Jana Hladuvková、Jirí Gregor、Tomáš Rada、Lenka Kubicová、Vera Klimešová、Jarmila Kaustová

  DOI：10.1002/(sici)1521-4184(199801)331:1<3::aid-ardp3>3.0.co;2-2

  日期：1998.1

  6,8‐dibromo‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐dione, substituted on the phenyl ring, was prepared by the reaction of the corresponding salicylanilides with ethyl chloroformate. The compounds were evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. Their activity increases with increasing hydrophobicity and electron‐withdrawing

  6,8-二氯-3-苯基-2H-苯并恶嗪-2,4(3H)-二酮的八种衍生物和6,8-二溴-3-苯基-2H-1,3-苯并恶嗪-的九种衍生物苯环上取代的 2,4 (3H)-二酮是通过相应的水杨酰苯胺与氯甲酸乙酯反应制备的。在体外评估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抗分枝杆菌活性。它们的活性随着苯环上取代基的疏水性和吸电子能力的增加而增加。
• Design, Synthesis, and Biological Activities of Closantel Analogues: Structural Promiscuity and Its Impact on <i>Onchocerca volvulus</i>
  作者：Amanda L. Garner、Christian Gloeckner、Nancy Tricoche、Joseph S. Zakhari、Moses Samje、Fidelis Cho-Ngwa、Sara Lustigman、Kim D. Janda

  DOI：10.1021/jm200364n

  日期：2011.6.9

  Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.