5-(4-chlorophenyl)-3-(2-morpholinoethyl)imino-2-(3-pyridyl)amino-3,5-dihydrophenazine | 1353737-60-6

• 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-(2-morpholinoethyl)imino-2-(3-pyridyl)amino-3,5-dihydrophenazine
• 英文别名: 5-(4-chlorophenyl)-3-(2-morpholin-4-ylethylimino)-N-pyridin-3-ylphenazin-2-amine
• CAS: 1353737-60-6
• 化学式: C₂₉H₂₇ClN₆O
• 分子量: 511.026
• InChiKey: RNVODBQQKDBPHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-3-(2-morpholinoethyl)imino-2-(3-pyridyl)amino-3,5-dihydrophenazine 在 盐酸 作用下， 以 乙醇 为溶剂， 以249 mg的产率得到5-(4-chlorophenyl)-3-((2-morpholinoethyl)imino)-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine trihydrochloride
  参考文献：
  名称：

  新型亲水性瑞米诺嗪作为有效的抗原生动物剂。

  摘要：

  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。

  DOI：

  10.1002/cmdc.201900522
• 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 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 5-(4-chlorophenyl)-3-(2-morpholinoethyl)imino-2-(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

• 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.
• 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。