2',3'-dideoxy-2'-fluororibosylhypoxanthine | 134892-26-5

• 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: 2',3'-dideoxy-2'-fluororibosylhypoxanthine
• 英文别名: 2'-Fluoro-2',3'-dideoxyinosine；9-[(2R,3R,5S)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 134892-26-5
• 化学式: C₁₀H₁₁FN₄O₃
• 分子量: 254.221
• InChiKey: SLWSQPYUSBXANQ-BAJZRUMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [(2S,4R,5R)-5-(6-氨基嘌呤-9-基)-4-氟四氢呋喃-2-基]甲醇 在 adenosine deaminase (EC 3.5.4.4) from calf intestinal mucosa 作用下， 以85%的产率得到2',3'-dideoxy-2'-fluororibosylhypoxanthine
  参考文献：
  名称：

  cycloSal-Pronucleotides of 2‘-Fluoro-ara- and 2‘-Fluoro-ribo-2‘,3‘- dideoxyadenosine as a Strategy to Bypass a Metabolic Blockade

  摘要：

  Novel, lipophilic cycloSal triesters 4a-c and 5a-c were synthesized, respectively, from the ara- and ribo-configurated 2'-fluorinated-2',3'-dideoxyadenosines 2 and 3. The cycloSal phosphotriesters were used as tools to study the effects of the two different sugar pucker conformations induced by two opposite configurations of the fluorine substituent at C2' of the dideoxyribose moiety. F-ara-ddA (2) is known to be an active anti-HIV agent, whereas the ribo-analogue 3 is inactive. Hydrolysis studies with the triester precursors 4a-c and 5a-c showed selective formation of the monophosphates of 2 and 3. The lipophilicity of the triester prodrugs was considerably increased by the cycloSal mask with respect to ddA (1), F-ara-ddA (2), and F-ribo-ddA (3). Phosphotriesters 4 and 5 proved to be completely resistant to ADA and AMPDA deamination. In parallel experiments, ribo-nucleoside 3 showed a 50-fold faster deamination rate relative to the ara-analogue 2. Against HIV in CEM cells, the phosphotriesters 4 proved to be 10-fold more potent than the parent nucleoside 2. Furthermore, the prodrugs 4 were active against MSV-induced transformation of C3H/3T3 fibroblasts, while 2 was inactive. More interestingly, the ribo-configurated phosphotriesters 5, prepared from the inactive F-ribo-ddA (3), showed a level of anti-HIV activity that was even higher than that of F-ara-ddA (2). Our findings clearly prove that the application of the cycloSal-pronucleotide concept to F-ribo-ddA (3) overcomes a metabolic blockade in the formation of the corresponding monophosphate.

  DOI：

  10.1021/jm981097r

文献信息

• Methods and compositions for treating pain
  申请人：Moran M. Magdalene

  公开号：US20070219222A1

  公开（公告）日：2007-09-20

  The present application relates to compounds and methods for treating pain, incontinence and other conditions.

  本申请涉及化合物和治疗疼痛、失禁和其他疾病的方法。
• Compounds for modulating TRPV3 function
  申请人：Chong A. Jayhong

  公开号：US20070179164A1

  公开（公告）日：2007-08-02

  The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.

  本申请涉及化合物和治疗与TRPV3相关的疼痛和其他病症的方法。
• MESOPHASIC FORMS OF (3S)-AMINOMETHYL-5-METHYL-HEXANOIC ACID PRODRUGS AND METHODS OF USE
  申请人：Yao Fenmei

  公开号：US20090192222A1

  公开（公告）日：2009-07-30

  Mesophasic forms of (3S)-aminomethyl-5-hexanoic acid prodrugs and methods of preparing and methods of using mesophasic forms of (3S)-aminomethyl-5-hexanoic acid prodrugs are provided.

  本发明提供了(3S)-氨甲基-5-己酸前药的介相形式及其制备方法和使用方法。
• [EN] INHIBITION OF HIV USING SYNERGISTIC COMBINATIONS OF NUCLEOSIDE DERIVATIVES
  申请人：ONCOGEN LIMITED PARTNERSHIP

  公开号：WO1990011081A1

  公开（公告）日：1990-10-04

  (EN) The present invention relates to the use of synergistic combinations of nucleoside derivatives for inhibiting human immunodeficiency virus (HIV) replication, thereby limiting HIV infection. In a particular embodiment, the purine nucleoside analogue dideoxyinosine combined with the pyrimidine nucleoside analogue 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) exhibit strong synergistic activity and diminished cytotoxic activity toward mammalian cells.(FR) La présente invention concerne l'utilisatin de combinaisons à effet synergique de dérivés de nucléosides pour inhiber la réplication du virus d'immunodéficience humaine (HIV) et limiter ainsi l'infection par le HIV. Dans un mode de réalisation particulier, la didésoxyinosine analogue du nucléoside de purine, combinée avec la 2',3'-didésoxy-2'-3'- didéshydrothymidine (d4T) analogue du nucléoside de pyrimidine, présente une forte activité synergique et diminue l'activité cytotoxique envers les cellules de mammifère.

  本发明涉及使用核苷酸衍生物的协同组合物来抑制人类免疫缺陷病毒（HIV）的复制，从而限制HIV感染。在一个特定的实施例中，嘌呤核苷类似物二脱氧肌苷与嘧啶核苷类似物2'，3'-二脱氧-2'，3'-二脱氢胸腺嘧啶（d4T）表现出强烈的协同作用，并对哺乳动物细胞的细胞毒性活性降低。
• Therapeutic azide compounds
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US20010036930A1

  公开（公告）日：2001-11-01

  Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

  提供了药物前药组成物，其中包括具有可在体内转化为药物的药物的偶氮衍生物。具有胺基，酮基和羟基取代基的药物的偶氮衍生物在体内转化为相应的药物，增加了药物的半衰期。此外，偶氮前药通常比相应的药物更能穿过血脑屏障。特别有用的是cordycepin，2'-F-ara-ddI，AraA，acyclovir，penciclovir和相关药物的偶氮衍生物。有用的偶氮前药是治疗性脂环烷胺，酮和羟基取代化合物的偶氮衍生物，包括芳基烷基，杂环芳基烷基和环状脂肪族化合物，其中胺基或氧原子基团位于环上，或胺基或氧原子基团位于脂肪侧链上，以及治疗性嘌呤和嘧啶，核苷类似物和磷酸化核苷类似物。