N¹-(5-fluoro-2,4-dinitrophenyl)-N²-phenylbenzene-1,2-diamine | 512178-35-7

• 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: N¹-(5-fluoro-2,4-dinitrophenyl)-N²-phenylbenzene-1,2-diamine
• 英文别名: 3-fluoro-4,6-dinitro-2'-anilinodiphenylamine；2-N-(5-fluoro-2,4-dinitrophenyl)-1-N-phenylbenzene-1,2-diamine
• CAS: 512178-35-7
• 化学式: C₁₈H₁₃FN₄O₄
• 分子量: 368.324
• InChiKey: SVALTMYRRVVJSW-UHFFFAOYSA-N

物化性质

• 沸点：
  519.2±50.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N¹-(5-fluoro-2,4-dinitrophenyl)-N²-phenylbenzene-1,2-diamine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 28.0h， 生成 2-N-(2-anilinophenyl)-4-N-pyridin-3-ylbenzene-1,2,4,5-tetramine
  参考文献：
  名称：

  Identification of Less Lipophilic Riminophenazine Derivatives for the Treatment of Drug-Resistant Tuberculosis

  摘要：

  Clofazimine (CFZ), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (MDR-TB). CFZ has several side effects which can be attributed to its extremely high lipophilicity. A series of novel riminophenazine analogues bearing a C-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity. All compounds were evaluated for their in vitro activity and cytotoxicity. The results demonstrated that many new compounds had potent activity against M. tuberculosis with MICs of less than 0.03 mu g/mL and low cytotoxicity with IC50 values greater than 64 mu g/mL. Some compounds were tested for in vivo efficacy against MDR-TB in an experimental mouse infection model. Two compounds demonstrated equivalent or better efficacy than CFZ in this model with significantly reduced skin discoloration potential.

  DOI：

  10.1021/jm300828h
• 作为产物：
  描述：

  2-硝基二苯胺 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 4.5h， 生成 N¹-(5-fluoro-2,4-dinitrophenyl)-N²-phenylbenzene-1,2-diamine
  参考文献：
  名称：

  Identification of Less Lipophilic Riminophenazine Derivatives for the Treatment of Drug-Resistant Tuberculosis

  摘要：

  Clofazimine (CFZ), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (MDR-TB). CFZ has several side effects which can be attributed to its extremely high lipophilicity. A series of novel riminophenazine analogues bearing a C-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity. All compounds were evaluated for their in vitro activity and cytotoxicity. The results demonstrated that many new compounds had potent activity against M. tuberculosis with MICs of less than 0.03 mu g/mL and low cytotoxicity with IC50 values greater than 64 mu g/mL. Some compounds were tested for in vivo efficacy against MDR-TB in an experimental mouse infection model. Two compounds demonstrated equivalent or better efficacy than CFZ in this model with significantly reduced skin discoloration potential.

  DOI：

  10.1021/jm300828h

文献信息

• Synthesis and Characterization of Isodiphenylfluorindone and Isodiphenylfluorindinone
  作者：Georgia A. Zissimou、Andreas Kourtellaris、Panayiotis A. Koutentis

  DOI：10.1021/acs.joc.8b00554

  日期：2018.4.20

  and isodiphenylfluorindinone 7 are synthesized. The former reacts with NaOMe to give the 13-methoxyisodiphenylfluorindone 22 (95%), while the latter reacts with 70% perchloric acid to give the bisperchlorate 21 (87%) and with MnO2 dimerizes to give 13,13′-bi(isodiphenylfluorindone) 4 (60%). UV–vis, NMR, CV, and DFT computational studies support the structural assignments of all products. Single-crystal

  合成异二苯基氟茚酮6和异二苯基氟茚酮7。用NaOMe前者发生反应，得到13-methoxyisodiphenylfluorindone 22（95％），同时用70％高氯酸后者进行反应，得到bisperchlorate 21（87％）中并用的MnO 2二聚化，得到13，13'-BI（isodiphenylfluorindone ）4（60％）。UV-vis，NMR，CV和DFT计算研究支持所有产品的结构分配。据报道异二苯基氟茚二酮7的单晶X射线衍射研究。
• Discovery of new riminophenazine analogues as antimycobacterial agents against drug-resistant Mycobacterium tuberculosis
  作者：Xiaoqiang Zhao、Yuheng Mei、Zhihao Guo、Shuyi Si、Xican Ma、Yinghong Li、Yan Li、Danqing Song

  DOI：10.1016/j.bioorg.2022.105929

  日期：2022.11

  for their antimycobacterial activities against Mycobacterium marinum. and M. tuberculosis H37Rv, taking clofazimine (1) as the lead. Structure-activity relationship (SAR) analysis revealed that the introduction of a heterocycle or diethylamine substituted benzene moiety on the N-5 atom might be beneficial for activity. The most potent compound 7m also displayed enhanced activity against both wild-type

  制备了 23 种新的 riminophenazine 和 pyrido[3,2-b]quinoxaline 衍生物，并检查了它们对海分枝杆菌的抗分枝杆菌活性。和结核分枝杆菌H37Rv，以氯法齐明( 1 )为先导。构效关系 (SAR) 分析表明，在N -5 原子上引入杂环或二乙胺取代的苯部分可能对活性有益。最有效的化合物7m对野生型以及耐多药 (MDR) 和广泛耐药 (XDR) TB 临床分离株也表现出增强的活性，MIC 范围为 0.08 至 1.25 μg/mL，尤其对菌株 M20A507，抗1 . 进一步的机制研究表明，其抗结核活性与细胞膜破坏无关，但与 NDH-2 减少和由此产生的高 ROS 产生有关。我们的研究为进一步将氯法齐明衍生物开发成有前景的抗 MDR 和 XDR TB 的抗菌剂提供了指导。
• Clofazimine analogs with antileishmanial and antiplasmodial activity
  作者：Anna Barteselli、Manolo Casagrande、Nicoletta Basilico、Silvia Parapini、Chiara M. Rusconi、Michele Tonelli、Vito Boido、Donatella Taramelli、Fabio Sparatore、Anna Sparatore

  DOI：10.1016/j.bmc.2014.11.028

  日期：2015.1

  A set of novel riminophenazine derivatives has been synthesized and evaluated for in vitro activity against chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains of Plasmodium falciparum and against different species of Leishmania promastigotes. Most of the new compounds inhibited the growth of Leishmania promastigotes as well as CQ-S and CQ-R strains of P. falciparum with IC50 in submicromolar range, resulting in the best cases 1-2 orders of magnitude more potent than the parent compound clofazimine. (C) 2014 Elsevier Ltd. All rights reserved.
• Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism
  作者：Xintong Zhang、Yulong Shi、Zhihao Guo、Xiaoqiang Zhao、Jiajing Wu、Shouchun Cao、Yonghua Liu、Yuhua Li、Weijin Huang、Youchun Wang、Qiang Liu、Yinghong Li、Danqing Song

  DOI：10.1016/j.ejmech.2022.114209

  日期：2022.4