4-benzoyl-3-carboxamido-1-(β-D-ribofuranosyl)-1,4-dihydropyridine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-benzoyl-3-carboxamido-1-(β-D-ribofuranosyl)-1,4-dihydropyridine
• 英文别名: 4-benzoyl-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4H-pyridine-3-carboxamide
• 化学式: C₁₈H₂₀N₂O₆
• 分子量: 360.367
• InChiKey: PVXGQEWNUIBZQY-QECSNABOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4-吡啶二酰亚胺 在 盐酸胍 、 sodium methylate 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 6.42h， 生成 4-benzoyl-3-carboxamido-1-(β-D-ribofuranosyl)-1,4-dihydropyridine
  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

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.