[(2S,4S,5R)-4-氟-5-嘌呤-9-基四氢呋喃-2-基]甲醇 | 132722-90-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: [(2S,4S,5R)-4-氟-5-嘌呤-9-基四氢呋喃-2-基]甲醇
• 英文名称: 9-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)-9H-purine
• 英文别名: 9-(2,3-dideoxy-2-fluoro-β-D-arabinofuranosyl)purine；9-(2,3-Dideoxy-2-fluoro-β-D-arabinofuranosyl)-purine；9-(2',3'-Dideoxy-2'-fluoroarabinofuranosyl)purine；[(2S,4S,5R)-4-fluoro-5-purin-9-yloxolan-2-yl]methanol
• CAS: 132722-90-8
• 化学式: C₁₀H₁₁FN₄O₂
• 分子量: 238.221
• InChiKey: FDVQUYZZLFRUIS-MHYGZLNHSA-N

物化性质

• 沸点：
  460.1±55.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2S,4S,5R)-4-氟-5-嘌呤-9-基四氢呋喃-2-基]甲醇 在 phosphate buffer 、 xanthine oxidase 作用下， 生成 9-[(2R,3S,5S)-3-氟-5-(羟基甲基)四氢呋喃-2-基]-3H-嘌呤-6-酮
  参考文献：
  名称：

  Enhanced Brain Delivery of an Anti-HIV Nucleoside 2'-F-ara-ddI by Xanthine Oxidase Mediated Biotransformation

  摘要：

  In order to enhance the brain delivery of 2'-F-ara-ddI, 2'-F-ara-ddP 6 was synthesized and its in vitro and in vivo bioconversion reaction studied. For the study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5-benzoyl-1,2-0-isopropylidene-3-deoxyribose 1. For in vitro study 2'-F-ara-ddP was incubated in pH 2, mouse liver homogenate, and mouse serum at 37-degrees-C. No degradation was observed in pH 2 and serum, while in liver homogenate 2'-F-ara-ddP was almost completely converted to 2'-F-ara-ddI within 20 min (t1/2 = 3.54 min). In order to determine the role of xanthine oxidase in the conversion of 2'-F-ara-ddP to 2'-F-ara-ddI, in vitro studies were conducted in phosphate buffer (pH 7.4) in the presence or absence of allopurinol, in which the half-lives of 2'-F-ara-ddP were 7.4 and 3.4 h, respectively, indicating the conversions were catalyzed by the xanthine oxidase. A similar experiment with aldehyde oxidase isolated from the human liver did not affect the biotransformation. The biotransformation was also detected in the brain homogenate, although the rate of conversion was low and incomplete. In order to assess the bioconversion in vivo, pharmacokinetic studies of 2'-F-ara-ddP and 2'-F-ara-ddI were conducted in mice. The maximum serum concentrations of 2'-F-ara-ddI administered itself and as 2'-F-ara-ddP reached 48.1 +/- 10.00 and 89.3 +/- 26.0 muM and were observed in 1 and 0.25 h, respectively. The data indicate that 2'-F-ara-ddI is absorbed at a slower rate than that of 2'-F-ara-ddP. The bioavailability of the prodrug after oral administration was 60.7 %. The concentration of 2'-F-ara-ddI following oral administration of 2'-ara-ddI was close to the detection limits while 2'-F-ara-ddI was detected at significantly higher concentrations in the brain after oral administration of 2'-F-ara-ddP. From this study, we have administered the enhanced brain delivery of anti-HIV nucleoside utilizing an in vivo biotransformation system.

  DOI：

  10.1021/jm00032a017
• 作为产物：
  描述：

  Dithiocarbonic acid O-[(2R,3R,4S,5R)-2-(tert-butyl-dimethyl-silanyloxymethyl)-4-fluoro-5-purin-9-yl-tetrahydro-furan-3-yl] ester S-methyl ester 在 偶氮二异丁腈 、 三正丁基氢锡 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 0.75h， 生成 [(2S,4S,5R)-4-氟-5-嘌呤-9-基四氢呋喃-2-基]甲醇
  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

• EP0540686A4
  申请人：——

  公开号：EP0540686A4

  公开（公告）日：1993-05-26
• 2'-FLUOROFURANOSYL DERIVATIVES AND NOVEL METHOD OF PREPARING 2'-FLUOROPYRIMIDINE AND 2'-FLUOROPURINE NUCLEOSIDES
  申请人：THE UNITED STATES OF AMERICA, represented by THE SECRETARY, UNITED STATES DEPARTMENT OF COMMERCE

  公开号：EP0540686A1

  公开（公告）日：1993-05-12
• 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.