2-(1-methoxy-5-isoquinolineamino)-3-nitrobenzoic acid | 369652-59-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(1-methoxy-5-isoquinolineamino)-3-nitrobenzoic acid
• 英文别名: 2-[(1-methoxyisoquinolin-5-yl)amino]-3-nitrobenzoic acid
• CAS: 369652-59-5
• 化学式: C₁₇H₁₃N₃O₅
• 分子量: 339.307
• InChiKey: LLKOWHLLUPHART-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(1-methoxy-5-isoquinolineamino)-3-nitrobenzoic acid 在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 反应 3.0h， 以62%的产率得到4-methoxypyrido[4,3-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+
• 作为产物：
  描述：

  1-氯异喹啉 在 palladium on activated charcoal 、 copper(l) iodide 、 铜 N-乙基吗啉 、 硫酸 、 氢气 、 硝酸 、 potassium nitrate 、 三乙胺 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 4.5h， 生成 2-(1-methoxy-5-isoquinolineamino)-3-nitrobenzoic 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。
• US6552021B2
  申请人：——

  公开号：US6552021B2

  公开（公告）日：2003-04-22