1-Methyl-1H-pyrazolo[3,4-alpha]phenazine-10-carboxylic acid (2-dimethylamino-ethyl)-amide

• 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: 1-Methyl-1H-pyrazolo[3,4-alpha]phenazine-10-carboxylic acid (2-dimethylamino-ethyl)-amide
• 英文别名: N-[2-(dimethylamino)ethyl]-1-methylpyrazolo[3,4-a]phenazine-10-carboxamide
• 化学式: C₁₉H₂₀N₆O
• 分子量: 348.407
• InChiKey: OKRIKDYVMDGFJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-硝基吲唑 在 palladium on activated charcoal 、 copper(l) iodide 、 铜 N-乙基吗啉 、 sodium hydroxide 、 sodium tetrahydroborate 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 0.5h， 生成 1-Methyl-1H-pyrazolo[3,4-alpha]phenazine-10-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+

文献信息

• Pharmaceutical compounds
  申请人：Xenova Limited

  公开号：US06552021B2

  公开（公告）日：2003-04-22

  A compound which is a heteroaromatic[a]phenazine carboxamide derivative of formula (I) wherein X is a five- or six-membered heteroaromatic ring which contains one or two nitrogen atoms and which is unsubstituted or substituted by C1-C6 alkyl, hydroxyl or C1-C6 alkoxy; Q is C1-C6 alkylene which is unsubstituted or substituted by C1-C6 alkyl which is unsubstituted or substituted by a hydroxy group; and R1 and R2 which are the same or different are each C1-C6 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.

  一种杂环芳香族苯并吡嗪羧酰胺衍生物化合物，其化学式为（I），其中X为一个含有一个或两个氮原子的五元或六元杂环芳香族环，未取代或取代为C1-C6烷基，羟基或C1-C6烷氧基；Q为未取代或取代为C1-C6烷基的C1-C6烷基，该C1-C6烷基未取代或取代为羟基；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，可用于治疗肿瘤，包括表达MDR的肿瘤。