6-(α-D-ribofuranosyl)picolinamide | 117134-31-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(α-D-ribofuranosyl)picolinamide
• 英文别名: 6-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyridine-2-carboxamide
• CAS: 117134-31-3
• 化学式: C₁₁H₁₄N₂O₅
• 分子量: 254.243
• InChiKey: XXWRCZSAYAYIDH-ZYUZMQFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4:3,5-di-O-benzylidene-D-aldehydo-ribose 在 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 正丁基锂 、 氨 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 3.33h， 生成 6-(α-D-ribofuranosyl)picolinamide
  参考文献：
  名称：

  核苷。CXLVIII。6-（。BETA.-D-呋喃呋喃糖基）吡啶啉酰胺的合成。D-核糖内酯的新型C-核苷。

  摘要：

  用2-溴-6-硫代吡啶处理2、4：3、5-二-O-亚苄基-D-醛-核糖（1），得到6-（2，4：3）的同分异构体和同分异构体的混合物，5-二-O-亚苄基-D-戊醇-1-基）-2-溴吡啶（分别为2和3）。对这些异构体进行色谱分离。通过2的1′-羟基的甲磺化，然后用三氟乙酸处理，将化合物2转化为6-（β-D-呋喃呋喃糖基）-2-溴吡啶（6）。用类似的方法，由3制备α-异构体7。七步也由市售D-核糖内酯合成了相同的吡啶-C-核苷6和7。将2和3的溴官能团转化进入羧酰胺基团，得到6-（2，4：3，5-二-O-亚苄基-D-戊糖醇-1-基）吡啶啉酰胺（10）及其同分异构体11。将10进行甲磺酸化，然后进行三氟乙酸处理，得到6-（β-D-呋喃呋喃糖基）吡啶甲酸酰胺（14）。对11的相似处理得到了α对应物15。

  DOI：

  10.1248/cpb.36.634

文献信息

• Antiviral agents for treatment of Flaviviridae infections
  申请人：——

  公开号：US20040266723A1

  公开（公告）日：2004-12-30

  The disclosed invention is a composition for and a method of treating Flaviviridae ( Hepacivirus, Flavivirus, Pestivirus ) infections, including BVDV and HCV, in a host, including animals, and especially humans, using a small molecule or its pharmaceutically acceptable salt or prodrug.

  本发明是一种用于治疗以下疾病的组合物和方法 病毒科 ( 病毒(Hepacivirus, Flavivirus, Pestivirus) )感染的组合物和方法，包括使用小分子或其药学上可接受的盐或原药治疗宿主（包括动物，特别是人类）的BVDV和HCV感染。
• 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.
• PANKIEWICZ, KRZYSZTOF W.;KABAT, MAREK M.;SOCHACKA, ELZBIETA;CISZEWSKI, LE+, NUCLEOSIDES AND NUCLEOTIDES, 7,(1988) N-6, C. 589-593
  作者：PANKIEWICZ, KRZYSZTOF W.、KABAT, MAREK M.、SOCHACKA, ELZBIETA、CISZEWSKI, LE+

  DOI：——

  日期：——
• KABAT, MAREK M.;PANKIEWICZ, KRZYSZTOF W.;SOCHACKA, ELZBIETA;WATANABE, KYO+, CHEM. AND PHARM. BULL., 36,(1988) N 2, 634-640
  作者：KABAT, MAREK M.、PANKIEWICZ, KRZYSZTOF W.、SOCHACKA, ELZBIETA、WATANABE, KYO+

  DOI：——

  日期：——
• ANTIVIRAL AGENTS FOR TREATMENT OF FLAVIVIRIDAE INFECTIONS
  申请人：Pharmasset Limited

  公开号：EP1366055A2

  公开（公告）日：2003-12-03