pyrido[2,3-a]-phenazine-11-carboxylic acid | 401916-15-2

• 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: pyrido[2,3-a]-phenazine-11-carboxylic acid
• 英文别名: Pyrido[2,3-a]phenazine-11-carboxylic acid
• CAS: 401916-15-2
• 化学式: C₁₆H₉N₃O₂
• 分子量: 275.266
• InChiKey: BLYQYOXITLIQQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  pyrido[2,3-a]-phenazine-11-carboxylic acid 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 1,7,12-Triaza-benzo[a]anthracene-11-carboxylic acid (2-dimethylamino-ethyl)-amide
  参考文献：
  名称：

  Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

  摘要：

  Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-alpha]phenazines. A 4-methoxypyrido[4,3-alpha]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.

  DOI：

  10.1021/jm010330+
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸 在 N-乙基吗啉 、 sodium tetrahydroborate 、 copper(l) iodide 、 sodium ethanolate 、 铜 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 50.0h， 生成 pyrido[2,3-a]-phenazine-11-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

  摘要：

  Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-alpha]phenazines. A 4-methoxypyrido[4,3-alpha]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.

  DOI：

  10.1021/jm010330+

文献信息

• Pharmaceutical compounds
  申请人：——

  公开号：US20010034346A1

  公开（公告）日：2001-10-25

  A compound which is a heteroaromatic[a]phenazine carboxamide derivative of formula (I) 1 wherein X is a five- or six-membered heteroaromatic ring which contains one or two nitrogen atoms and which is unsubstituted or substituted by C 1 -C 6 alkyl, hydroxyl or C 1 -C 6 alkoxy; Q is C 1 -C 6 alkylene which is unsubstituted or substituted by C 1 -C 6 alkyl which is unsubstituted or substituted by a hydroxy group; and R 1 and R 2 which are the same or different are each C 1 -C 6 alkyl; or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of topoisomerase I and II and can be used to treat tumours, including tumours which express MDR.

  该化合物是公式（I）的杂环芳香基苯并吡嗪羧酰胺衍生物，其中X是一个含有一个或两个氮原子的五元或六元杂环芳香环，未取代或取代为C1-C6烷基，羟基或C1-C6烷氧基; Q是未取代或取代为C1-C6烷基（未取代或取代为羟基基团）的C1-C6烷基; R1和R2相同或不同，均为C1-C6烷基; 或其药学上可接受的盐。这些化合物是拓扑异构酶I和II的抑制剂，并可用于治疗肿瘤，包括表达MDR的肿瘤。
• Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents
  作者：Swarna A. Gamage、Julie A. Spicer、Gordon W. Rewcastle、John Milton、Sukhjit Sohal、Wendy Dangerfield、Prakash Mistry、Nigel Vicker、Peter A. Charlton、William A. Denny

  DOI：10.1021/jm010330+

  日期：2002.1.1

  Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-alpha]phenazines. A 4-methoxypyrido[4,3-alpha]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.