5-(β-D-ribofuranosyl)nicotinamide-(5'-5'')-adenosine pyrophosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 5-(β-D-ribofuranosyl)nicotinamide-(5'-5'')-adenosine pyrophosphate
• 英文别名: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5S)-5-(5-carbamoylpyridin-1-ium-3-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• 化学式: C₂₁H₂₇N₇O₁₄P₂
• 分子量: 663.431
• InChiKey: UINNILASBHZOTM-KMXXXSRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  327
• 氢给体数：
  8
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  5-[(2S,3R,4S,5R)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]吡啶-3-甲酰胺 在 三正丁胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 5-(β-D-ribofuranosyl)nicotinamide-(5'-5'')-adenosine pyrophosphate
  参考文献：
  名称：

  NAD analogs. 1. Synthesis of isosteric analogs of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide

  摘要：

  Two isosteric analogues of nicotinamide adenine dinucleotide, C-NAD (11) and C-PAD (12), in which the nicotinamide riboside portion is replaced by a C-nucleoside, were synthesized from 5-(beta-D-ribofuranosyl)nicotinamide (7) and 6-(beta-D-ribofuranosyl)picolinamide (8), respectively. Nucleoside 7 was prepared from the 2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-D-ribonolactone (13) and 3-cyano-5-lithiopyridine as reported earlier. Nucleoside 8 was obtained by conversion of the bromo function of the 6-(2,3:4,5-di-O-isopropylidene-D-altro-pentitol-1-yl)-2-bromopyridine (14) into a carboxamido group followed by mesylation of the anomeric hydroxyl group to give derivative 18. Treatment of 18 with CF3COOH/CHCl3 caused deisopropylidenation with simultaneous cyclization into the desired 6-(beta-D-ribofuranosyl)picolinamide (8). NAD analogues, C-NAD (11) and C-PAD (12), were synthesized by imidazole-catalyzed coupling of the corresponding 5'-monophosphates of 7 and 8 with the adenosine-5'-monophosphate. Dinucleotide 11 was found to inhibit the proliferation of L1210 cells (IC50 = 7 muM) and to be a good competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH, ID50 = 20 muM) as well as bovine glutamate dehydrogenase (GDH, K(i) = 15 muM). Interestingly, C-NAD (11) caused extremely potent noncompetitive inhibition of horse liver alcohol dehydrogenase (ADH, K(i) = 1.1 nM), whereas C-PAD (12) was found to be a much less potent competitive inhibitor (K(i) = 20 muM) of ADH.

  DOI：

  10.1021/jm00065a008

文献信息

• NAD analogs. 1. Synthesis of isosteric analogs of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide
  作者：Krzysztof W. Pankiewicz、Joanna Zeidler、Lech A. Ciszewski、J. Ellis Bell、Barry M. Goldstein、Hiremagalur N. Jayaram、Kyoichi A. Watanabe

  DOI：10.1021/jm00065a008

  日期：1993.6

  Two isosteric analogues of nicotinamide adenine dinucleotide, C-NAD (11) and C-PAD (12), in which the nicotinamide riboside portion is replaced by a C-nucleoside, were synthesized from 5-(beta-D-ribofuranosyl)nicotinamide (7) and 6-(beta-D-ribofuranosyl)picolinamide (8), respectively. Nucleoside 7 was prepared from the 2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-D-ribonolactone (13) and 3-cyano-5-lithiopyridine as reported earlier. Nucleoside 8 was obtained by conversion of the bromo function of the 6-(2,3:4,5-di-O-isopropylidene-D-altro-pentitol-1-yl)-2-bromopyridine (14) into a carboxamido group followed by mesylation of the anomeric hydroxyl group to give derivative 18. Treatment of 18 with CF3COOH/CHCl3 caused deisopropylidenation with simultaneous cyclization into the desired 6-(beta-D-ribofuranosyl)picolinamide (8). NAD analogues, C-NAD (11) and C-PAD (12), were synthesized by imidazole-catalyzed coupling of the corresponding 5'-monophosphates of 7 and 8 with the adenosine-5'-monophosphate. Dinucleotide 11 was found to inhibit the proliferation of L1210 cells (IC50 = 7 muM) and to be a good competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH, ID50 = 20 muM) as well as bovine glutamate dehydrogenase (GDH, K(i) = 15 muM). Interestingly, C-NAD (11) caused extremely potent noncompetitive inhibition of horse liver alcohol dehydrogenase (ADH, K(i) = 1.1 nM), whereas C-PAD (12) was found to be a much less potent competitive inhibitor (K(i) = 20 muM) of ADH.