2-chloro-3-[(2,5-dimethoxyphenyl)amino]naphthalene-1,4-dione | 331462-39-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-chloro-3-[(2,5-dimethoxyphenyl)amino]naphthalene-1,4-dione
• 英文别名: 2-Chloro-3-(2,5-dimethoxyanilino)naphthoquinone；2-chloro-3-(2,5-dimethoxyanilino)naphthalene-1,4-dione
• CAS: 331462-39-6
• 化学式: C₁₈H₁₄ClNO₄
• 分子量: 343.766
• InChiKey: OSINQNFUFPGLGB-UHFFFAOYSA-N

物化性质

• 熔点：
  146.7-146.9 °C
• 沸点：
  474.3±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-3-[(2,5-dimethoxyphenyl)amino]naphthalene-1,4-dione 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以29%的产率得到1,4-dimethoxybenzo[b]phenazine-6,11-dione
  参考文献：
  名称：

  Synthesis andIn VitroBiological Evaluation of Aminonaphthoquinones and Benzo[b]phenazine-6,11-dione Derivatives as Potential Antibacterial and Antifungal Compounds

  摘要：

  一系列2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）通过2,3-二氯-1,4-萘醌与芳胺基（2a-h）和苯并[b]苝啉-6,11-二酮衍生物（4a-c）反应合成，方法是将2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）与叠氮化钠处理后进行检测其体外抗菌和抗真菌活性。结果表明，化合物3d和3g对白念珠菌（MIC = 78.12 μg/mL）具有强效的抗真菌活性。所有合成的化合物（3a-h，4a-c）对肠球菌具有活性，MIC值在312.5和1250 μg/mL之间。苯并[b]苝啉-6,11-二酮衍生物（4a-c）主要对革兰氏阳性细菌活性较强。这一系列新成员的结构是基于它们的光谱特性（红外光谱，1H核磁共振，13C核磁共振和质谱）确定的。

  DOI：

  10.1155/2015/645902
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 2,5-二甲氧基苯胺 以 乙醇 为溶剂， 生成 2-chloro-3-[(2,5-dimethoxyphenyl)amino]naphthalene-1,4-dione
  参考文献：
  名称：

  Synthesis andIn VitroBiological Evaluation of Aminonaphthoquinones and Benzo[b]phenazine-6,11-dione Derivatives as Potential Antibacterial and Antifungal Compounds

  摘要：

  一系列2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）通过2,3-二氯-1,4-萘醌与芳胺基（2a-h）和苯并[b]苝啉-6,11-二酮衍生物（4a-c）反应合成，方法是将2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）与叠氮化钠处理后进行检测其体外抗菌和抗真菌活性。结果表明，化合物3d和3g对白念珠菌（MIC = 78.12 μg/mL）具有强效的抗真菌活性。所有合成的化合物（3a-h，4a-c）对肠球菌具有活性，MIC值在312.5和1250 μg/mL之间。苯并[b]苝啉-6,11-二酮衍生物（4a-c）主要对革兰氏阳性细菌活性较强。这一系列新成员的结构是基于它们的光谱特性（红外光谱，1H核磁共振，13C核磁共振和质谱）确定的。

  DOI：

  10.1155/2015/645902

文献信息

• 2-Phenylaminonaphthoquinones and related compounds: Synthesis, trypanocidal and cytotoxic activities
  作者：Ivan Sieveking、Pablo Thomas、Juan C. Estévez、Natalia Quiñones、Mauricio A. Cuéllar、Juan Villena、Christian Espinosa-Bustos、Angélica Fierro、Ricardo A. Tapia、Juan D. Maya、Rodrigo López-Muñoz、Bruce K. Cassels、Ramon J. Estévez、Cristian O. Salas

  DOI：10.1016/j.bmc.2014.07.030

  日期：2014.9

  A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against

  合成了一系列新的2-氨基萘醌和相关化合物，并在体外评估了其为锥虫和细胞毒剂。一些经过测试的化合物抑制了前鞭毛体的生长和锥鞭毛体的生存能力。与目前的锥虫杀灭药硝呋替莫相比，几种化合物显示出相似或更高的活性和选择性。与Vero细胞相比，化合物4l对尼古丁对克鲁斯锥虫的选择性更高。测试了一些合成的醌类对癌细胞和正常成纤维细胞的影响，表明萘醌部分的某些化学修饰可诱导并显着提高细胞毒性的选择性指数（4g和10）。此处给出的结果表明，2-氨基萘醌衍生物的抗T. cruzi活性可以通过用吡啶部分取代苯环来提高。有趣的是，C-3上存在氯原子和高度亲脂性烷基或芳环是新近观察到的元素，应导致发现更具选择性的细胞毒性和锥虫性化合物。
• Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents
  作者：Julio Benites、Jaime A. Valderrama、Karina Bettega、Rozangela Curi Pedrosa、Pedro Buc Calderon、Julien Verrax

  DOI：10.1016/j.ejmech.2010.10.006

  日期：2010.12

  Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells) and healthy fibroblasts (BALB/3T3) were assessed in vitro using the MTT reduction assay 48 h after drug exposure. SAR analysis of the aminonaphthoquinone series showed that insertion of a chlorine atom in the acceptor quinone nucleus and/or insertion of a methyl group at the nitrogen atom of the donor phenylamino group induced significant changes in cytotoxic activity. Quinones 7 and 9, which exhibited the highest selective indexes (5.73 and 6.29, respectively), were further characterized using the following assays: Colony formation, caspase-3 activity, and ATP content. The results showed that aminoquinone 7 strongly influenced ATP levels and impaired the proliferative capacity of T24 cells without activating caspase-3. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis and<i>In Vitro</i>Biological Evaluation of Aminonaphthoquinones and Benzo[<i>b</i>]phenazine-6,11-dione Derivatives as Potential Antibacterial and Antifungal Compounds
  作者：Amaç Fatih Tuyun、Nilüfer Bayrak、Hatice Yıldırım、Nihal Onul、Emel Mataraci Kara、Berna Ozbek Celik

  DOI：10.1155/2015/645902

  日期：——

  A series of 2-arylamino-3-chloro-1,4-naphthoquinone derivatives (3a–h) by the reaction of 2,3-dichloro-1,4-naphthoquinone with aryl amines (2a–h) and benzo[b]phenazine-6,11-dione derivatives (4a–c) by the treatment of 2-arylamino-3-chloro-1,4-naphthoquinone derivatives (3a–h) with sodium azide were synthesized and tested for theirin vitroantibacterial and antifungal activities. The results suggest that compounds3dand3ghad potent antifungal activity againstCandida albicans(MIC = 78.12 μg/mL). All synthesized compounds (3a–h,4a–c) possessed activity againstE. faecaliswith MIC values of between 312.5 and 1250 μg/mL. Benzo[b]phenazine-6,11-dione derivatives (4a–c) were mostly active against Gram-positive bacteria. The structures of the new members of the series were established on the basis of their spectral properties (IR,¹H NMR,¹³C NMR, and mass spectrometry).

  一系列2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）通过2,3-二氯-1,4-萘醌与芳胺基（2a-h）和苯并[b]苝啉-6,11-二酮衍生物（4a-c）反应合成，方法是将2-芳胺基-3-氯-1,4-萘醌衍生物（3a-h）与叠氮化钠处理后进行检测其体外抗菌和抗真菌活性。结果表明，化合物3d和3g对白念珠菌（MIC = 78.12 μg/mL）具有强效的抗真菌活性。所有合成的化合物（3a-h，4a-c）对肠球菌具有活性，MIC值在312.5和1250 μg/mL之间。苯并[b]苝啉-6,11-二酮衍生物（4a-c）主要对革兰氏阳性细菌活性较强。这一系列新成员的结构是基于它们的光谱特性（红外光谱，1H核磁共振，13C核磁共振和质谱）确定的。
• Synthesis, Computational Study, and Evaluation of in vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives
  作者：Nilufer Bayrak、Hatice Yıldırım、Amac Tuyun、Emel Kara、Berna Celik、Girish Gupta、Hamid Nasiri

  DOI：10.2174/1570180813666161020164931

  日期：2016.10.20

  Background: A set of novel sulfanyl aminonaphthoquinone derivatives (5a-j) were synthesized starting from 2,3-dichloro-1,4-naphthoquinone (1). The amine substituents were introduced via a nucleophilic substitution at reflux temperature. Subsequent reactions of 2-chloro-3-arylamino-1,4-naphthoquinones (3a-d) with different thiols (4a-c) led to the formation of the desired amino-and thio-substituted products (5a-j).Methods: The purity and identity of the synthesized compounds were verified with IR, H-1 and C-13 NMR, and MS spectroscopy. In vitro antimicrobial activity was evaluated in a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and one fungi with an additional study of antibiofilm activities. The anticancer activities of two selected compounds (5e and 5f) were evaluated against 60 human tumor cell lines derived from nine neoplastic diseases by National Cancer Institute (NCI).Results: As a result, compound (5e) was identified as a hit with antibacterial efficiency against human originated pathogens S. aureus with minimal inhibitory concentration (MIC) of 19.53 mu g/mL. When considering the antibiofilm activities of antibacterial molecule 5e against the S. aureus biofilms, the minimum biofilm eradication concentration (MBEC) value was 10000 mu g/mL. Concerning on anticancer activities, both compounds (5e and 5f) exhibited moderate anticancer activities on some of tumor cells, but no activity against normal peripheral blood mononuclear cells (PBMC). In addition, docking study was used to provide further insights into the experimental observations.Conclusion: Taken together, compound 5e could be considered as a promising starting point for further development.