N⁶-methyl-9H-(2-C-methyl-β-D-ribofuranosyl)adenine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-methyl-9H-(2-C-methyl-β-D-ribofuranosyl)adenine
• 英文别名: 9-(2'-C-methyl-β-D-ribofuranosyl)-6-N-methyladenine；β-D-2'-CH3-ribo-6-N-methylaminopurine；5-Hydroxymethyl-3-methyl-2-(6-methylamino-purin-9-yl)-tetrahydro-furan-3,4-diol；(2R,3R,4R,5R)-5-(hydroxymethyl)-3-methyl-2-[6-(methylamino)purin-9-yl]oxolane-3,4-diol
• 化学式: C₁₂H₁₇N₅O₄
• 分子量: 295.298
• InChiKey: VZNPPUSZNNZBJU-YUTYNTIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-Boc-L-缬氨酸 、 N⁶-methyl-9H-(2-C-methyl-β-D-ribofuranosyl)adenine 在 三乙胺 、 Carbonyldiimidazole 、 丙二酸 、 溶剂黄146 作用下， 以 DMF (N,N-dimethyl-formamide) 、 四氢呋喃 为溶剂， 以88%的产率得到(2R,3R,4R,5R)-4-hydroxy-2-(hydroxymethyl)-4-methyl-5-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuran-3-yl (tert-butoxycarbonyl)-L-valinate
  参考文献：
  名称：

  [EN] PROCESS FOR THE PRODUCTION OF 3'-NUCLEOSIDE PRODRUGS
  [FR] PROCEDE DE PRODUCTION DE PROMEDICAMENTS A BASE DE 3'-NUCLEOSIDES

  摘要：

  提供了一种用于选择性对核糖呋喃糖苷2'或3'-支链核苷的3'-酰化的单步过程。这些化合物可用作抗病毒药物，特别是可以用于治疗宿主中的黄病毒科感染。

  公开号：

  WO2004058792A1
• 作为产物：
  描述：

  6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 氨 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 22.0h， 生成 N⁶-methyl-9H-(2-C-methyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  Synthesis of 9-(2-β-C-methyl-β-d-ribofuranosyl)-6-substituted purine derivatives as inhibitors of HCV RNA replication

  摘要：

  A series of 9-(2'-beta-C-methyl-p-D-ribofuranosyl)-6-substituted purine derivatives were synthesized as potential inhibitors of HCV RNA replication. Their inhibitory activities in a cell based HCV replicon assay were reported. A prodrug approach was used to further improve the potency of these compounds by increasing the intracellular levels of 5'-monophosphate metabolites. These nucleotide prodrugs showed much improved inhibitory activities of HCV RNA replication. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.020

文献信息

• Antitumor Activity of <i>C</i>-Methyl-β-<scp>d</scp>-ribofuranosyladenine Nucleoside Ribonucleotide Reductase Inhibitors
  作者：Palmarisa Franchetti、Loredana Cappellacci、Michela Pasqualini、Riccardo Petrelli、Patrizia Vita、Hiremagalur N. Jayaram、Zsuzsanna Horvath、Thomas Szekeres、Mario Grifantini

  DOI：10.1021/jm048944c

  日期：2005.7.1

  A series of adenosine derivatives substituted at the 1'-, 2'-, or 3'-position of the ribose ring with a methyl group was synthesized and evaluated for antitumor activity. From this study 3'-C-methyladenosine (3'-Me-Ado) emerged as the most active compound, showing activity against human myelogenous leukemia K562, multidrug resistant human leukemia K562IU, human promyelocytic leukemia HL-60, human colon

  合成了一系列在核糖环的1'-，2'-或3'-位被甲基取代的腺苷衍生物，并评估了其抗肿瘤活性。通过这项研究，3'-C-甲基腺苷（3'-Me-Ado）作为最活跃的化合物出现，显示出对人骨髓性白血病K562，多药耐药性人白血病K562IU，人早幼粒细胞白血病HL-60，人结肠癌HT- 29和人类乳腺癌MCF-7细胞系，IC（50）值范围从11到38μM。结构-活性关系研究表明3'-Me-Ado的结构对于该活性至关重要。用小的烷基或环烷基取代N（6）-氨基的氢原子，在嘌呤环的2位引入氯原子，或甲基从3'位置移至其他核糖位置导致抗肿瘤活性降低或丧失。3'-Me-Ado的抗增殖活性似乎与其通过核糖核苷酸还原酶抑制作用同时耗尽细胞内嘌呤和嘧啶脱氧核苷酸的能力有关。
• PROCESS FOR THE PRODUCTION OF 3 -NUCLEOSIDE PRODRUGS
  申请人：Idenix (Cayman) Limited

  公开号：EP1575971A1

  公开（公告）日：2005-09-21
• EP1575971A4
  申请人：——

  公开号：EP1575971A4

  公开（公告）日：2008-03-05
• Process for the production of 3'-nucleoside prodrugs
  申请人：——

  公开号：US20040181051A1

  公开（公告）日：2004-09-16

  Provided is a single-step process for the selective 3′-acylation of a ribofuranosyl 2′ or 3′-branched nucleoside. These compounds are useful as antiviral agents, and in particular, can be used to treat Flaviviridae infections in a host in need thereof.
• Synthesis of 9-(2-β-C-methyl-β-d-ribofuranosyl)-6-substituted purine derivatives as inhibitors of HCV RNA replication
  作者：Yili Ding、Jean-Luc Girardet、Zhi Hong、Vicky C.H. Lai、Haoyun An、Yung-hyo Koh、Stephanie Z. Shaw、Weidong Zhong

  DOI：10.1016/j.bmcl.2004.11.020

  日期：2005.2

  A series of 9-(2'-beta-C-methyl-p-D-ribofuranosyl)-6-substituted purine derivatives were synthesized as potential inhibitors of HCV RNA replication. Their inhibitory activities in a cell based HCV replicon assay were reported. A prodrug approach was used to further improve the potency of these compounds by increasing the intracellular levels of 5'-monophosphate metabolites. These nucleotide prodrugs showed much improved inhibitory activities of HCV RNA replication. (C) 2004 Elsevier Ltd. All rights reserved.