(-)-(2R,4R)-2-Fluoro-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (-)-(2R,4R)-2-Fluoro-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine
• 英文别名: (-)-(2R,4R)-2-Fluoro-9-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]adenine；[(2R,4R)-4-(6-amino-2-fluoropurin-9-yl)-1,3-dioxolan-2-yl]methanol
• 化学式: C₉H₁₀FN₅O₃
• 分子量: 255.209
• InChiKey: CDNIAFXFMZPGPJ-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (-)-(2R,4R)-9-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-dioxolan-4-yl>-7-fluoroadenine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以85%的产率得到(-)-(2R,4R)-2-Fluoro-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine
  参考文献：
  名称：

  1,3-Dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes

  摘要：

  In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 muM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine greater-than-or-equal-to adenine greater-than-or-equal-to 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine congruent-to N6-methyladenine congruent-to 6-mercaptopurine congruent-to 6-(methylthio)purine.

  DOI：

  10.1021/jm00053a004

文献信息

• [EN] ENANTIOMERICALLY PURE beta -D-DIOXOLANE NUCLEOSIDES WITH SELECTIVE ANTI-HEPATITIS B VIRUS ACTIVITY<br/>[FR] NUCLEOSIDES DE beta -D-DIOXOLANE A PURETE ENANTIOMERE ET A ACTIVITE DIRIGEE SELECTIVEMENT CONTRE LE VIRUS DE L'HEPATITE B
  申请人：EMORY UNIVERSITY

  公开号：WO1994009793A1

  公开（公告）日：1994-05-11

  (EN) The invention is a method for the treatment of humans infected with HBV that includes administering an HBV treatment amount of an enatiomerically pure $g(b)-D-dioxolanyl purine nucleoside of formula (I), wherein R is OH, Cl, NH2 or H, and X is selected from the group consisting of alkyl, acyl, monophosphate, diphosphate, and triphosphate, or its pharmaceutically acceptable salt.(FR) Procédé de traitement des malades atteints du virus de l'hépatite B. Il consiste à administrer une dose efficace d'un nucléoside de $g(b)-D-dioxolanyl purine à pureté énantiomère de la formule (I), dans laquelle R représente OH, Cl, NH2 ou H; et X est sélectionné dans le groupe constitué d'alkyle, acyle, monophosphate, diphosphate, triphosphate, ou son sel pharmaceutiquement acceptable.

  该发明是一种治疗感染HBV的人类的方法，包括给予纯对映体$g(b)-D-二氧杂环己基嘌呤核苷的HBV治疗剂量，其化学式为(I)，其中R为OH，Cl，NH2或H，X选择自烷基，酰基，单磷酸，二磷酸和三磷酸的群，或其药学上可接受的盐。
• Enantiomerically pure beta-D-dioxolane-nucleosides
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP1081148A2

  公开（公告）日：2001-03-07

  A method and composition for the treatment of humans infected with HIV that includes administration of an HIV treatment amount of an enantiomerically pure β-D-dioxolanyl purine nucleoside of formula (I), wherein R is OH, Cl, NH2, or H, or a pharmaceutically acceptable salt or derivative of the compound, optionally in a pharmaceutically acceptable carrier or diluent.

  一种用于治疗感染艾滋病毒的人类的方法和组合物，包括施用对映体纯的式（I）β-D-二氧戊环嘌呤核苷的艾滋病毒治疗量，其中 R 是 OH、Cl、NH2 或 H，或该化合物的药学上可接受的盐或衍生物，可选地在药学上可接受的载体或稀释剂中。
• ENANTIOMERICALLY PURE $g(b)-D-DIOXOLANE-NUCLEOSIDES
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP0656778A1

  公开（公告）日：1995-06-14
• EP0656778A4
  申请人：——

  公开号：EP0656778A4

  公开（公告）日：1995-08-02
• ENANTIOMERICALLY PURE BETA-D-DIOXOLANE-NUCLEOSIDES
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP0656778B1

  公开（公告）日：2001-05-30