5-(4-chlorophenyl)-3-imino-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine | 1353740-44-9

• 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: 5-(4-chlorophenyl)-3-imino-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine
• 英文别名: 5-(4-chlorophenyl)-3-imino-N-pyridin-3-ylphenazin-2-amine
• CAS: 1353740-44-9
• 化学式: C₂₃H₁₆ClN₅
• 分子量: 397.867
• InChiKey: HBSUGRWVEOCVHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-3-imino-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 4.0h， 生成 5-(4-chlorophenyl)-3-{[4-(octahydro-1H-quinolizin-9a-yl)butyl]imino}-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine trihydrochloride
  参考文献：
  名称：

  Clofazimine analogs with antileishmanial and antiplasmodial activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.11.028
• 作为产物：
  描述：

  2-硝基-4-氯二苯基胺 在 溶剂黄146 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 5-(4-chlorophenyl)-3-imino-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine
  参考文献：
  名称：

  Systematic Evaluation of Structure-Activity Relationships of the Riminophenazine Class and Discovery of a C2 Pyridylamino Series for the Treatment of Multidrug-Resistant Tuberculosis

  摘要：

  克洛法嗪是苯嗪类药物的重要成员，是治疗麻风的基石药物。该药目前正在临床试验中研究治疗多药耐药性结核病，以应对迫切需要的新药，以克服现有和新出现的药物耐药性。然而，克洛法嗪在结核病治疗中的使用受到其高脂溶性和皮肤色素沉着副作用的困扰。为了识别新一代脂溶性较低且不易染色的苯嗪类药物，同时保持疗效，我们进行了系统的结构-活性关系（SAR）研究，通过合成多种克洛法嗪的类似物并评估其抗结核活性。研究表明，中心三环苯嗪系统和附加的芳环对抗结核活性具有重要作用。然而，连接在克洛法嗪的C2和N5位置的苯基可以被吡啶基替代，从而提供具有改进的物理化学性质和药代动力学特征的类药物。将连接在C2位置的苯基替换为吡啶基导致了一系列前景良好的新化合物，这些化合物具有更好的物理化学性质、增强的抗结核效能以及减少的色素沉着潜力。

  DOI：

  10.3390/molecules17044545

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。
• Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents
  作者：Ivan Bassanini、Silvia Parapini、Nicoletta Basilico、Anna Sparatore

  DOI：10.1002/cmdc.201900522

  日期：2019.11.20

  well on BMDM cell lines. Most of the new compounds potently inhibited the growth of both genera of protozoa with IC50 values in the high nanomolar range and good selectivities versus mammalian cells. Besides their potent activity against asexual intraerythrocytic stages of P. falciparum, three compounds showed potential as transmission-blocking agents. The key role of the hydrophilic C-2 aminopyridinyl

  SAR研究了一组新型的亲水性C-2氨基吡啶基嘧啶吩嗪类化合物，它们在C-3处具有各种官能化的基本侧链。评价了该新型化合物对两种不同种类的利什曼原虫前鞭毛体，巨噬细胞内利什曼原虫amastigotes，对氯喹敏感和对氯喹具有抗性的恶性疟原虫菌株以及对成熟阶段恶性疟原虫配子体细胞的体外活性。在BMDM细胞系上也评估了它们的细胞毒性。大多数新化合物都有效抑制原生动物两个属的生长，其IC50值在高纳摩尔范围内，并且相对于哺乳动物细胞具有良好的选择性。除了它们对恶性疟原虫无性红细胞内阶段的有效活性外，三种化合物还显示出潜在的传递阻断剂。
• 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。
• 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.