[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4R,5R)-5-[(4S)-3-carbamoyl-4-(pyridin-4-ylcarbonyl)-1,4-dihydropyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy})phosphinic acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: [({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4R,5R)-5-[(4S)-3-carbamoyl-4-(pyridin-4-ylcarbonyl)-1,4-dihydropyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy})phosphinic acid
• 英文别名: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-[(4S)-3-carbamoyl-4-(pyridine-4-carbonyl)-4H-pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
• 化学式: C₂₇H₃₂N₈O₁₅P₂
• 分子量: 770.543
• InChiKey: GZPCDCKLGMEXOS-BGARNJTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  52
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  348
• 氢给体数：
  8
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  异烟肼 、 β-烟酰胺腺嘌呤二核苷酸 在 manganese(ll) chloride 、 horse radish peroxidase 作用下， 以 phosphate buffer 为溶剂， 生成 Isoniazid-NAD 、 [({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4R,5R)-5-[(4S)-3-carbamoyl-4-(pyridin-4-ylcarbonyl)-1,4-dihydropyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy})phosphinic acid 、 Isonicotinic-acetyl-nicotinamide-adenine dinucleotide
  参考文献：
  名称：

  Spontaneous Formation of the Bioactive Form of the Tuberculosis Drug Isoniazid

  摘要：

  It works even without the enzyme: The formation of the bioactive form 1 of isoniazid inside Mycobacterium tuberculosis does not depend on specific interactions within the active site of the inhibited enzyme, but rather relies on the fast addition of acyl radicals to electron-deficient heterocycles such as NAD(+).

  DOI：

  10.1002/(sici)1521-3773(19990903)38:17<2588::aid-anie2588>3.0.co;2-8

文献信息

• 1H and 13C NMR Characterization of Hemiamidal Isoniazid-NAD(H) Adducts as Possible Inhibitors Of InhA Reductase of Mycobacterium tuberculosis
  作者：Sylvain Broussy、Yannick Coppel、Michel Nguyen、Jean Bernadou、Bernard Meunier

  DOI：10.1002/chem.200204637

  日期：2003.5.9

  of INH inside the bacteria Mycobacterium tuberculosis. Performed in the presence of NAD(+), this oxidation generates a family of isomeric INH-NAD(H) adducts, which have been shown to be effective inhibitors of InhA, an enzyme essential in mycolic acid biosynthesis. In this work, we fully characterized by (1)H and (13)C NMR spectroscopy four main species of INH-NAD(H) adducts that coexist in solution

  异烟肼（INH）易于被焦磷酸锰（III）氧化，焦磷酸锰是参与结核分枝杆菌内INH活化的KatG蛋白的化学模型。在NAD（+）的存在下进行该氧化反应，生成了一系列异构的INH-NAD（H）加合物，已证明它们是InhA（霉菌酸生物合成必不可少的酶）的有效抑制剂。在这项工作中，我们通过（1）H和（13）C NMR光谱充分表征了溶液中共存的四种主要INH-NAD（H）加合物。它们中的两个是开放的非对映异构体，其由烟酰胺辅酶的第四位上的异烟酰基团的共价连接组成。另外两个是环化反应的结果，其中涉及烟酰胺的酰胺基和异烟酰酰基的羰基，得到非对映异构的半缩醛。尽管X射线晶体学已在InhA的活性位点表征了具有4S构型的INH-NAD（H）加合物，并且该结合的加合物被解释为开放形式（Rozwarski等，Science 1998，279，98-102），提出有关INH-NAD（H）加合物的有效活性形式（开放或循
• Spontaneous Formation of the Bioactive Form of the Tuberculosis Drug Isoniazid
  作者：Martin Wilming、Kai Johnsson

  DOI：10.1002/(sici)1521-3773(19990903)38:17<2588::aid-anie2588>3.0.co;2-8

  日期：1999.9.3

  It works even without the enzyme: The formation of the bioactive form 1 of isoniazid inside Mycobacterium tuberculosis does not depend on specific interactions within the active site of the inhibited enzyme, but rather relies on the fast addition of acyl radicals to electron-deficient heterocycles such as NAD(+).