5-chloro-2-hydroxy-N-(2-methyl-4-nitrophenyl)benzamide | 90426-01-0

• 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: 5-chloro-2-hydroxy-N-(2-methyl-4-nitrophenyl)benzamide
• CAS: 90426-01-0
• 化学式: C₁₄H₁₁ClN₂O₄
• 分子量: 306.705
• InChiKey: PCTYLSQYQZTRHP-UHFFFAOYSA-N

物化性质

• 沸点：
  425.2±45.0 °C(Predicted)
• 密度：
  1.483±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-chloro-2-hydroxy-N-(2-methyl-4-nitrophenyl)benzamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer

  摘要：

  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。

  DOI：

  10.3390/ph16050735

文献信息

• [EN] CHEMICAL MODULATORS OF SIGNALING PATHWAYS AND THERAPEUTIC USE<br/>[FR] MODULATEURS CHIMIQUES DES VOIES DE SIGNALISATION ET UTILISATION THÉRAPEUTIQUE
  申请人：UNIV DUKE

  公开号：WO2016210289A1

  公开（公告）日：2016-12-29

  Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial and viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

  描述了治疗与Wnt/Frizzled信号通路失调相关的疾病的方法。这些方法包括识别需要治疗的对象，给予Wnt/Frizzled信号通路抑制剂，包括这些抑制剂的药物组合物，以及使用这些化合物和组合物治疗癌症、细菌和病毒感染、红斑狼疮、2型糖尿病、非酒精性脂肪肝炎（NASH）和非酒精性脂肪肝病（NAFLD）的方法。
• Synthesis and antimicrobial activity of salicylanilide derivatives. II.
  作者：ISAO OZAWA、ISAO TAKEUCHI、KAZUKO YAMAMOTO、YOSHIKI HAMADA、TOMIYOSHI ITO、MASAO KUWAHARA、TATSUO TAKAGAKI

  DOI：10.1248/cpb.32.305

  日期：——

  The condensation of 4-halo-o-toluidine with salicylic acid or 5-halosalicylic acid was carried out by the use of phosphorus trichloride in xylene to obtain the salicylanilides 1-13, 4-Halo (or nitro)-o-toluidine, 4-halo-o-nitroaniline or 2, 4-dihaloaniline was condensed with 3, 5-dihalosalicylic acid to provide the salicylanilides 14-30 by the same method. The salicylanilides 2-15, 26 and 27 gave the acetylated compounds 31-46 on treatment with acetic anhydride and pyridine. The salicylanilides 26 and 27 gave the methylated compounds 47 and 48 on treatment with dimethyl sulfate. In the antimicrobial activity tests of the synthesized compounds, 4', 5-dihalo-2'-methylsalicylanilides 1-13 and the acetylated compounds 31-42 showed strong antimicrobial activity against some Eumycetes at the minimum inhibitory concentration (MIC) of 0.8 μg/ml. Compound 3 was shown to have a strong preventive activity against downy mildew of cucumber.

  用三氯化磷在二甲苯中缩合 4-卤代邻甲苯胺与水杨酸或 5-卤代水杨酸，得到水杨酰苯胺 1-13；用同样的方法缩合 4-卤代（或硝基）邻甲苯胺、4-卤代-硝基苯胺或 2，4-二卤苯胺与 3，5-二卤水杨酸，得到水杨酰苯胺 14-30。水杨酰苯胺 2-15、26 和 27 经乙酸酐和吡啶处理后得到乙酰化化合物 31-46。用硫酸二甲酯处理水杨酰苯胺 26 和 27 后，可得到甲基化化合物 47 和 48。在合成化合物的抗菌活性测试中，4', 5-二卤-2'-甲基水杨酰苯胺 1-13 和乙酰化化合物 31-42 对一些真菌有很强的抗菌活性，最低抑菌浓度（MIC）为 0.8 μg/ml。化合物 3 对黄瓜霜霉病具有很强的预防活性。
• Chemical modulators of signaling pathways and therapeutic use
  申请人：Duke University

  公开号：US10905665B2

  公开（公告）日：2021-02-02

  Described are methods of treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway. The methods include identifying subjects in need of therapy, administering inhibitors of the Wnt/Frizzled signaling pathway, pharmaceutical compositions including the inhibitors, and methods of using the compounds and compositions for treating cancer, bacterial and viral infection, lupus, type II diabetes, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a subject.

  描述了治疗与 Wnt/Frizzled 信号通路失调有关的疾病的方法。这些方法包括鉴定需要治疗的受试者、施用 Wnt/Frizzled 信号通路抑制剂、包括抑制剂的药物组合物，以及使用化合物和组合物治疗受试者的癌症、细菌和病毒感染、狼疮、II 型糖尿病、非酒精性脂肪性肝炎（NASH）和非酒精性脂肪肝（NAFLD）的方法。
• &lt;p&gt;Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs&lt;/p&gt;
  作者：Jens Hagenow、Stefanie Hagenow、Kathrin Grau、Mohammad Khanfar、Lena Hefke、Ewgenij Proschak、Holger Stark

  DOI：10.2147/dddt.s236586

  日期：——

  Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors.Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results.Results: N-(2,4-Dinitrophenyl)benzo [d] [1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC50 = 56 nM, K-i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites.Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.
• CHEMICAL MODULATORS OF SIGNALING PATHWAYS AND THERAPEUTIC USE
  申请人：Duke University

  公开号：EP3313388A1

  公开（公告）日：2018-05-02