8-methyl-9-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)adenine | 132722-94-2

• 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: 8-methyl-9-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)adenine
• 英文别名: 9-(2,3-Dideoxy-2-fluoro-β-D-arabinofuranosyl)-8-methyl-6-aminopurine；9-(2,3-Dideoxy-2-fluoro-beta-D-arabinofuranosyl)-8-methyladenine；[(2S,4S,5R)-5-(6-amino-8-methylpurin-9-yl)-4-fluorooxolan-2-yl]methanol
• CAS: 132722-94-2
• 化学式: C₁₁H₁₄FN₅O₂
• 分子量: 267.263
• InChiKey: QNGHOQJBOWPNPR-OKTBNZSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-amino-9-<5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl>-9H-purine 在 溶剂黄146 、 lithium diisopropyl amide 作用下， 反应 1.25h， 生成 8-methyl-9-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)adenine
  参考文献：
  名称：

  Potential anti-AIDS drugs. Lipophilic, adenosine deaminase-activated prodrugs

  摘要：

  Selected acid-stable (2'-fluoro-2',3'-dideoxyarabinofuranosyl)adenine nucleosides containing methyl groups and other lipophilic functions at various positions in the adenine ring were prepared and evaluated as anti-HIV agents. The N6-methyl (1f), N6-benzoyl (1g), and 6-chloro (li) analogues had modest activity, giving 30-50% protection to ATH8 cells infected with HIV. 2-Methyl (1d), 8-methyl (1h), and 2,N6-dimethyl (1e) substitution, as well as N1-oxide (21) formation, abolished the activity of the parent compound (1a). Several of these compounds, originally designed as agents for treating HIV in the central nervous system, were further investigated as substrates for adenosine deaminase (ADA). Kinetic experiments showed that ADA catalyzed the formation of the anti-HIV active inosine compound 1b from the N6-methyl analogue 1f in a quantitative manner. The anti-HIV activity of 1f and 1i was abolished when the ADA inhibitor, 2'-deoxycoformycin, was added to the test mixture. In contrast, the activity of 1f was significantly enhanced when ADA was added to the test system. These data indicate that 1f and 1i are prodrug forms of 1b in systems containing ADA.

  DOI：

  10.1021/jm00109a018

文献信息

• 2'-FLUOROFURANOSYL DERIVATIVES AND NOVEL METHOD OF PREPARING 2'-FLUOROPYRIMIDINE AND 2'-FLUOROPURINE NUCLEOSIDES
  申请人：THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce

  公开号：EP0540686B1

  公开（公告）日：1995-08-30
• US5336764A
  申请人：——

  公开号：US5336764A

  公开（公告）日：1994-08-09
• US5817799A
  申请人：——

  公开号：US5817799A

  公开（公告）日：1998-10-06
• [EN] 2'-FLUOROFURANOSYL DERIVATIVES AND NOVEL METHOD OF PREPARING 2'-FLUOROPYRIMIDINE AND 2'-FLUOROPURINE NUCLEOSIDES
  申请人：——

  公开号：WO1992001700A1

  公开（公告）日：1992-02-06

  [EN] The instant invention is drawn to 2'-fluoroarabinofuranosyl compounds and a process for preparing same.
  [FR] L'invention concerne des composés de 2'-fluoroarabinofuranosyle et un procédé de préparation de ces composés.
• Potential anti-AIDS drugs. Lipophilic, adenosine deaminase-activated prodrugs
  作者：Joseph J. Barchi、Victor E. Marquez、John S. Driscoll、Harry Ford、Hiroaki Mitsuya、Takuma Shirasaka、Shizuko Aoki、James A. Kelley

  DOI：10.1021/jm00109a018

  日期：1991.5

  Selected acid-stable (2'-fluoro-2',3'-dideoxyarabinofuranosyl)adenine nucleosides containing methyl groups and other lipophilic functions at various positions in the adenine ring were prepared and evaluated as anti-HIV agents. The N6-methyl (1f), N6-benzoyl (1g), and 6-chloro (li) analogues had modest activity, giving 30-50% protection to ATH8 cells infected with HIV. 2-Methyl (1d), 8-methyl (1h), and 2,N6-dimethyl (1e) substitution, as well as N1-oxide (21) formation, abolished the activity of the parent compound (1a). Several of these compounds, originally designed as agents for treating HIV in the central nervous system, were further investigated as substrates for adenosine deaminase (ADA). Kinetic experiments showed that ADA catalyzed the formation of the anti-HIV active inosine compound 1b from the N6-methyl analogue 1f in a quantitative manner. The anti-HIV activity of 1f and 1i was abolished when the ADA inhibitor, 2'-deoxycoformycin, was added to the test mixture. In contrast, the activity of 1f was significantly enhanced when ADA was added to the test system. These data indicate that 1f and 1i are prodrug forms of 1b in systems containing ADA.