5-[(ethoxycarbonyl)methyl]-1-hydroxy-3-oxo-1-phenyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridinium bromide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-[(ethoxycarbonyl)methyl]-1-hydroxy-3-oxo-1-phenyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridinium bromide
• 英文别名: ethyl 2-(1-hydroxy-3-oxo-1-phenyl-2H-pyrrolo[3,4-c]pyridin-5-ium-5-yl)acetate;bromide
• 化学式: Br*C₁₇H₁₇N₂O₄
• 分子量: 393.237
• InChiKey: ZFZWIWFUOGVYPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.52
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[(ethoxycarbonyl)methyl]-1-hydroxy-3-oxo-1-phenyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridinium bromide 在 sodium tetrahydroborate 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以85%的产率得到ethyl (1-hydroxy-3-oxo-1-phenyl-1,2,4,5-tetrahydro-3H-pyrrolo[3,4-c]pyridin-5-yl)acetate
  参考文献：
  名称：

  The First Chemical Synthesis of the Core Structure of the Benzoylhydrazine−NAD Adduct, a Competitive Inhibitor of the Mycobacterium tuberculosis Enoyl Reductase

  摘要：

  An isoniazid-NAD adduct has been recently proposed as the ultimate metabolite responsible for the antituberculous activity of isoniazid (INH). Its structure results from binding of the isonicotinoyl radical at C4 position of the nicotinamide ring of NAD with further possible and debated cyclization to form a cyclic hemiamidal derivative. Replacing the pyridine cycle of INH in INH-NAD adduct by a phenyl cycle (BH-NAD adduct) was shown previously to still retain the activity. On these bases, the core structure (4-benzoyl-1,4-dihydronicotinamide ribonucleoside) of the BH-NAD adduct and a series of analogues have been synthesized by using 3,4-pyridinedicarboximide as starting material. Depending on the nature of the substituent (pyridine or aryl) and on the oxidized or the reduced state of the nicotinamide nucleus, they were found either in a cyclized hemiamidal or an opened form or were shown to exist in equilibrium under cyclized or opened forms. Although none of these compounds could significantly inhibit activity of the InhA or MabA reductases (two possible targets of isoniazid), they represent attractive targets to develop potential second-generation inhibitors, including the total chemical synthesis of the bioactive BH-NAD adduct.

  DOI：

  10.1021/jo051901z
• 作为产物：
  描述：

  N,N-二甲基苯甲酰胺 在 manganese(IV) oxide 、 ammonium hydroxide 、 sodium tetrahydroborate 、 甲酸 、 氯化亚砜 、 sodium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正庚烷 、 乙基苯 、 丙酮 为溶剂， 反应 72.75h， 生成 5-[(ethoxycarbonyl)methyl]-1-hydroxy-3-oxo-1-phenyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridinium bromide
  参考文献：
  名称：

  Studies on the 4-benzoylpyridine-3-carboxamide entity as a fragment model of the Isoniazid–NAD adduct

  摘要：

  构建 4-苯甲酰基吡啶框架的关键步骤是采用正交金属化亲电取代序列。研究发现，4-苯甲酰基吡啶-3-甲酰胺和一种 N-吡啶烷基化衍生物都以独特的环化半酰胺结构存在，而不是通常预期的酮酰胺开放形式。这些结构代表了参与抗结核药物异烟肼作用机制的异烟肼-NAD加合物的片段模型。

  DOI：

  10.1039/b415439h

文献信息

• The First Chemical Synthesis of the Core Structure of the Benzoylhydrazine−NAD Adduct, a Competitive Inhibitor of the <i>Mycobacterium tuberculosis</i> Enoyl Reductase
  作者：Sylvain Broussy、Vania Bernardes-Génisson、Annaïk Quémard、Bernard Meunier、Jean Bernadou

  DOI：10.1021/jo051901z

  日期：2005.12.1

  An isoniazid-NAD adduct has been recently proposed as the ultimate metabolite responsible for the antituberculous activity of isoniazid (INH). Its structure results from binding of the isonicotinoyl radical at C4 position of the nicotinamide ring of NAD with further possible and debated cyclization to form a cyclic hemiamidal derivative. Replacing the pyridine cycle of INH in INH-NAD adduct by a phenyl cycle (BH-NAD adduct) was shown previously to still retain the activity. On these bases, the core structure (4-benzoyl-1,4-dihydronicotinamide ribonucleoside) of the BH-NAD adduct and a series of analogues have been synthesized by using 3,4-pyridinedicarboximide as starting material. Depending on the nature of the substituent (pyridine or aryl) and on the oxidized or the reduced state of the nicotinamide nucleus, they were found either in a cyclized hemiamidal or an opened form or were shown to exist in equilibrium under cyclized or opened forms. Although none of these compounds could significantly inhibit activity of the InhA or MabA reductases (two possible targets of isoniazid), they represent attractive targets to develop potential second-generation inhibitors, including the total chemical synthesis of the bioactive BH-NAD adduct.
• Studies on the 4-benzoylpyridine-3-carboxamide entity as a fragment model of the Isoniazid–NAD adduct
  作者：Sylvain Broussy、Vania Bernardes-Génisson、Heinz Gornitzka、Jean Bernadou、Bernard Meunier

  DOI：10.1039/b415439h

  日期：——

  An ortho-metallation–electrophilic substitution sequence was employed as a key step to build the 4-benzoylpyridine framework. It was found that 4-benzoylpyridine-3-carboxamide and an N-pyridyl alkylated derivative both exist in a unique cyclized hemiamidal structure, not in the usually expected keto-amide open form. These structures represent fragment models of the Isoniazid–NAD adducts involved in the mechanism of action of the antituberculous drug Isoniazid.

  构建 4-苯甲酰基吡啶框架的关键步骤是采用正交金属化亲电取代序列。研究发现，4-苯甲酰基吡啶-3-甲酰胺和一种 N-吡啶烷基化衍生物都以独特的环化半酰胺结构存在，而不是通常预期的酮酰胺开放形式。这些结构代表了参与抗结核药物异烟肼作用机制的异烟肼-NAD加合物的片段模型。