5-(hydroxymethyl)-11-methyl-6H-pyrido<4,3-b>carbazole | 108320-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-(hydroxymethyl)-11-methyl-6H-pyrido<4,3-b>carbazole
• 英文别名: 5-hydroxymethyl-11-methyl-6H-pyrido<4,3-b>carbazole；11-methyl-6H-pyrido<4,3-b>carbazol-5-ylmethanol；11-methyl-6H-pyrido[4,3-b]carbazole-5-methanol；13-hydroxyellipticine；ellipticine；5-hydroxymethyl-11-methyl-6H-pyrido[4,3-b]carbazole；6H-Pyrido(4,3-b)carbazole, 5-(hydroxymethyl)-11-methyl-；(11-methyl-6H-pyrido[4,3-b]carbazol-5-yl)methanol
• CAS: 108320-78-1
• 化学式: C₁₇H₁₄N₂O
• 分子量: 262.311
• InChiKey: FCJUAVNKXJUAIX-UHFFFAOYSA-N

物化性质

• 熔点：
  257-258 °C (decomp)
• 沸点：
  563.5±45.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  48.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(hydroxymethyl)-11-methyl-6H-pyrido<4,3-b>carbazole 在 manganese(IV) oxide 作用下， 以 氯仿 为溶剂， 反应 3.5h， 以23 mg的产率得到11-甲基-6H-吡啶并[4,3-b]咔唑-5-甲醛
  参考文献：
  名称：

  一些6H-吡啶并[4,3-b]咔唑的合成及生物学性质。

  摘要：

  重新检查了甲基取代对玫瑰树碱生物学特性的影响。合成了9-羟基-6H-吡啶并[4,3-b]咔唑，在小鼠P388淋巴细胞白血病中没有抗肿瘤活性。合成了5-（羟甲基）-11-甲基-6H-吡啶并[4,3-b]咔唑（46）及其N-甲基氨基甲酸酯（48），并比较了它们对HeLa细胞中大分子合成的影响及其抗肿瘤特性。玫瑰树碱的那些。与生物碱1和羟甲基衍生物46产生部分可逆的[3H]胸苷掺入抑制作用相比，氨基甲酸酯不可逆地阻止了ti化嘧啶的掺入。该酯在P388淋巴细胞白血病中也比1或46更有效。

  DOI：

  10.1021/jm00390a014
• 作为产物：
  描述：

  椭圆玫瑰树碱 在 硝酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.75h， 生成 5-(hydroxymethyl)-11-methyl-6H-pyrido<4,3-b>carbazole
  参考文献：
  名称：

  玫瑰树碱合成的有效修饰和13-羟基玫瑰树碱的制备

  摘要：

  据报道，对先前公开的玫瑰树碱合成进行了简单的修改，其减少了反应时间并提高了产物的收率和纯度。研究了1，4-二甲基咔唑和玫瑰树碱衍生物的苯甲酰氧化反应，制备了13-羟基玫瑰树碱。

  DOI：

  10.1016/j.tetlet.2007.07.160

文献信息

• 9-substituted 6H-pyrido[4,3-b]carbazoles
  申请人：Rensselaer Polytechnic Institute

  公开号：US04851417A1

  公开（公告）日：1989-07-25

  Compounds comprising the series of 9-substituted 5-hydroxymethyl-11-methyl-6H-pyrido[4,3-b]carbazole N-alkyl or aryl carbamates of general structure: ##STR1## where R=H, lower alkoxy, OH, aryloxy R.sub.1 =H or lower alkyl R.sub.2 =lower alkyl or aryl.

  该化合物系列包括一般结构为9-取代的5-羟甲基-11-甲基-6H-吡啶[4,3-b]咔唑N-烷基或芳基氨基甲酸酯的化合物，其中：##STR1## 其中R=氢、低碳基氧、羟基、芳基氧，R.sub.1=氢或低碳基，R.sub.2=低碳基或芳基。
• Synthesis of 5-hydroxymethyl-11-methyl-6H-pyrido[4,3-b]carbazole and 5-formyl-11-methyl-6H-pyrido[4,3-b]carbazole (17-oxoellipticine)
  作者：Ross Bruce S、Archer Sydney

  DOI：10.1016/s0040-4039(00)85206-5

  日期：1986.1
• Ratcliffe, Andrew J.; Sainsbury, Malcolm; Smith, Andrew D., Journal of the Chemical Society. Perkin transactions I, 1988, p. 2933 - 2944
  作者：Ratcliffe, Andrew J.、Sainsbury, Malcolm、Smith, Andrew D.、Scopes, David I. C.

  DOI：——

  日期：——
• Cytochrome <i>b</i>₅ Increases Cytochrome P450 3A4-Mediated Activation of Anticancer Drug Ellipticine to 13-Hydroxyellipticine Whose Covalent Binding to DNA Is Elevated by Sulfotransferases and <i>N</i>,<i>O</i>-Acetyltransferases
  作者：Marie Stiborová、Radek Indra、Michaela Moserová、Věra Černá、Martina Rupertová、Václav Martínek、Tomáš Eckschlager、René Kizek、Eva Frei

  DOI：10.1021/tx3000335

  日期：2012.5.21

  The antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological efficiency is dependent on its cytochrome P450 (P450)- and/or peroxidase-mediated activation in target tissues. The P450 3A4 enzyme oxidizes ellipticine to five 3 metabolites, mainly to 13-hydroxy- and 12-hydroxyellipticine, the metabolites responsible for the formation of ellipticine-13-ylium and ellipticine-12-ylium ions that generate covalent DNA adducts. Cytochrome b(5) alters the ratio of ellipticine p metabolites formed by P450 3A4. While the amounts of the detoxication metabolites (7-hydroxy- and 9-hydroxyellipticine) were not changed with added cytochrome b(5), 12-hydroxy- and 13-hydroxyellipticine, and ellipticine N-2-oxide increased considerably. The P450 3A4-mediated oxidation of ellipticine was significantly changed only by holo-cytochrome 65, while apo-cytochrome b(5) without heme or Mn-cytochrome b(5) had no such effect. The change in amounts of metabolites resulted in an increased formation of covalent ellipticine-DNA adducts, one of the DNA-damaging mechanisms of ellipticine antitumor action. The amounts of 13-hydroxy- and 12-hydroxyellipticine formed by P450 3A4 were similar, but more than 7-fold higher levels of the adduct. were formed by 13-hydrox-yellipticine than by 12-hydroxyellipticine. The higher susceptibility of 13-hydroxyellipticine toward heterolytic dissociation to ellipticine-13-ylium in comparison to dissociation of 12-hydroxyellipticine to ellipticine-12ylium, determined by quantum chemical calculations, explains this phenomenon. The amounts of the 13-hydroxyellipticinederived DNA adduct significantly increased upon reaction of 13-hydroxyellipticine with either 3'-phosphoadenosine-5'phosphosulfate or acetyl-CoA catalyzed by human sulfotransferases 1A1, 1A2, 1A3, and 2A1, or N,O-acetyltransferases 1 and 2. The calculated reaction free energies of heterolysis of the sulfate and acetate esters are by 10-17 kcal/mol more favorable than the energy of hydrolysis of 13-hydroxyellipticine, which could explain the experimental data.
• ARCHER, SYDNEY
  作者：ARCHER, SYDNEY

  DOI：——

  日期：——