2',3'-dideoxy-5'-O-(trimethylacetyl)-5-fluorouridine | 107036-60-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2',3'-dideoxy-5'-O-(trimethylacetyl)-5-fluorouridine
• 英文别名: 2',3'-Dideoxy-5'-O-trimethylacetyl-5-fluorouridine；[(2S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl 2,2-dimethylpropanoate
• CAS: 107036-60-2
• 化学式: C₁₄H₁₉FN₂O₅
• 分子量: 314.314
• InChiKey: NRRDPJRCBWLQBU-WCBMZHEXSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2',3'-dideoxy-5'-O-(trimethylacetyl)-5-fluorouridine 在 劳森试剂 、 氨 作用下， 以 氯仿 、 苯 为溶剂， 110.0~138.0 ℃ 、1.72 MPa 条件下， 反应 26.0h， 生成 4-氨基-5-氟-1-[(2R,5S)-5-(羟基甲基)四氢呋喃-2-基]嘧啶-2-酮
  参考文献：
  名称：

  Potential anti-AIDS drugs. 2',3'-Dideoxycytidine analogs

  摘要：

  5-Substituted 2',3'-dideoxycytidine analogues have been synthesized and evaluated in vitro for their capabilities to protect T4+ lymphocytes from the cytopathic effects of the HTLV-III/LAV (HIV) virus, the causative agent of acquired immunodeficiency syndrome (AIDS). These analogues were designed to be more lipophilic than 2',3'-dideoxycytidine (ddC) in order to enhance central nervous system penetration. Earlier reports had shown that ddC is a potent protective agent. When ddC is substituted at the 5-position with either methyl or bromo substituents, activity is completely abolished. However, when the substitution is fluoro (5-F-ddC), both activity and potency are retained. 2',3'-Dideoxy-5-azacytidine is also protective but more toxic than ddC or 5-F-ddC. In a different approach, an attempt was made to utilize ddCMP, ddTMP, and ddAMP as preformed nucleotides in order to circumvent the generally low level of phosphorylation achieved with dideoxynucleosides which function as relatively poor substrates for the cellular kinases. Only ddAMP is as active as its nucleoside precursor. Because ddAMP is not more active than ddA at low concentrations, it is possible that the active agent is ddA which is generated from ddAMP prior to cell entry.

  DOI：

  10.1021/jm00388a020
• 作为产物：
  描述：

  5-氟-2'-脱氧脲核苷 在 吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 2.5h， 生成 2',3'-dideoxy-5'-O-(trimethylacetyl)-5-fluorouridine
  参考文献：
  名称：

  Potential anti-AIDS drugs. 2',3'-Dideoxycytidine analogs

  摘要：

  5-Substituted 2',3'-dideoxycytidine analogues have been synthesized and evaluated in vitro for their capabilities to protect T4+ lymphocytes from the cytopathic effects of the HTLV-III/LAV (HIV) virus, the causative agent of acquired immunodeficiency syndrome (AIDS). These analogues were designed to be more lipophilic than 2',3'-dideoxycytidine (ddC) in order to enhance central nervous system penetration. Earlier reports had shown that ddC is a potent protective agent. When ddC is substituted at the 5-position with either methyl or bromo substituents, activity is completely abolished. However, when the substitution is fluoro (5-F-ddC), both activity and potency are retained. 2',3'-Dideoxy-5-azacytidine is also protective but more toxic than ddC or 5-F-ddC. In a different approach, an attempt was made to utilize ddCMP, ddTMP, and ddAMP as preformed nucleotides in order to circumvent the generally low level of phosphorylation achieved with dideoxynucleosides which function as relatively poor substrates for the cellular kinases. Only ddAMP is as active as its nucleoside precursor. Because ddAMP is not more active than ddA at low concentrations, it is possible that the active agent is ddA which is generated from ddAMP prior to cell entry.

  DOI：

  10.1021/jm00388a020

文献信息

• DRISCOLL, JOHN S.;MARQUEZ, VICTOR E.;KIM, CHONG-HO;KELLEY, JAMES A.
  作者：DRISCOLL, JOHN S.、MARQUEZ, VICTOR E.、KIM, CHONG-HO、KELLEY, JAMES A.

  DOI：——

  日期：——
• US4788181A
  申请人：——

  公开号：US4788181A

  公开（公告）日：1988-11-29
• Potential anti-AIDS drugs. 2',3'-Dideoxycytidine analogs
  作者：Chong Ho Kim、Victor E. Marquez、Samuel Broder、Hiroaki Mitsuya、John S. Driscoll

  DOI：10.1021/jm00388a020

  日期：1987.5

  5-Substituted 2',3'-dideoxycytidine analogues have been synthesized and evaluated in vitro for their capabilities to protect T4+ lymphocytes from the cytopathic effects of the HTLV-III/LAV (HIV) virus, the causative agent of acquired immunodeficiency syndrome (AIDS). These analogues were designed to be more lipophilic than 2',3'-dideoxycytidine (ddC) in order to enhance central nervous system penetration. Earlier reports had shown that ddC is a potent protective agent. When ddC is substituted at the 5-position with either methyl or bromo substituents, activity is completely abolished. However, when the substitution is fluoro (5-F-ddC), both activity and potency are retained. 2',3'-Dideoxy-5-azacytidine is also protective but more toxic than ddC or 5-F-ddC. In a different approach, an attempt was made to utilize ddCMP, ddTMP, and ddAMP as preformed nucleotides in order to circumvent the generally low level of phosphorylation achieved with dideoxynucleosides which function as relatively poor substrates for the cellular kinases. Only ddAMP is as active as its nucleoside precursor. Because ddAMP is not more active than ddA at low concentrations, it is possible that the active agent is ddA which is generated from ddAMP prior to cell entry.