(E)-5-(4-fluorophenyl)-3-isopropylimino-2-(2-methoxy-3-pyridyl)amino-3,5-dihydrophenazine | 1401207-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (E)-5-(4-fluorophenyl)-3-isopropylimino-2-(2-methoxy-3-pyridyl)amino-3,5-dihydrophenazine
• CAS: 1401207-34-8
• 化学式: C₂₇H₂₄FN₅O
• 分子量: 453.519
• InChiKey: GBVYFZVFPAGNNG-JJKYIXSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.73
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.33
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  N 1-(4-fluorophenyl)benzene-1,2-diamine 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 20.0~110.0 ℃ 、275.8 kPa 条件下， 生成 (E)-5-(4-fluorophenyl)-3-isopropylimino-2-(2-methoxy-3-pyridyl)amino-3,5-dihydrophenazine
  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

• [EN] RIMINOPHENAZINES WITH 2-(HETEROARYL)AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY<br/>[FR] RIMINOPHÉNAZINES À SUBSTITUANTS 2-(HÉTÉROARYL)AMINO ET LEUR ACTIVITÉ ANTIMICROBIENNE
  申请人：GLOBAL ALLIANCE FOR TB DRUG DEV

  公开号：WO2012003190A1

  公开（公告）日：2012-01-05

  The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及具有杂芳基取代基的利米诺菲南类化合物，包括具有2-杂芳基氨基取代基的化合物，以及其制备方法，以及作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用，也可以与其他抗感染治疗联合使用。
• RIMINOPHENAZINES WITH 2-(HETEROARYL)AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY
  申请人：Liu Kai

  公开号：US20120071472A1

  公开（公告）日：2012-03-22

  The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及具有杂环芳基取代基的吡啶并吩嗪类化合物，包括那些具有2-杂环芳基氨基取代基的化合物，以及其制备方法和用作药物治疗结核分枝杆菌和其他微生物感染的用途，可以单独使用或与其他抗感染治疗药物联合使用。
• RIMINOPHENAZINES WITH 2-(HETEROARYL) AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY
  申请人：Global Alliance for TB Drug Development

  公开号：US20140243327A1

  公开（公告）日：2014-08-28

  The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments. A general representation of the 2-(heteroaryl)amino-riminophenazines is shown below.

  本发明涉及具有杂环芳基取代基的利米诺苯并嗪，包括具有2-杂环芳基氨基取代基的利米诺苯并嗪的制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的使用，可以单独使用或与其他抗感染治疗联合使用。下面是2-(杂环芳基)氨基利米诺苯并嗪的一般表示。
• US8716292B2
  申请人：——

  公开号：US8716292B2

  公开（公告）日：2014-05-06
• Identification of Less Lipophilic Riminophenazine Derivatives for the Treatment of Drug-Resistant Tuberculosis
  作者：Dongfeng Zhang、Yu Lu、Kai Liu、Binna Liu、Jingbin Wang、Gang Zhang、Hao Zhang、Yang Liu、Bin Wang、Meiqin Zheng、Lei Fu、Yanyan Hou、Ningbo Gong、Yang Lv、Chun Li、Christopher B. Cooper、Anna M. Upton、Dali Yin、Zhenkun Ma、Haihong Huang

  DOI：10.1021/jm300828h

  日期：2012.10.11

  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.