5'-O-(4,4'-dimethoxytrityl)-5-azacytidine | 107036-45-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(4,4'-dimethoxytrityl)-5-azacytidine
• 英文别名: 4-amino-1-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3,4-dihydroxyoxolan-2-yl]-1,3,5-triazin-2-one
• CAS: 107036-45-3
• 化学式: C₂₉H₃₀N₄O₇
• 分子量: 546.58
• InChiKey: CNRKHCBDJUMLBY-VEYUFSJPSA-N

物化性质

• 沸点：
  734.7±70.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-5-azacytidine 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 乙腈 为溶剂， 反应 26.0h， 生成 O-[(2R,3R,5S)-2-(4-amino-2-oxo-1,3,5-triazin-1-yl)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]oxolan-3-yl] imidazole-1-carbothioate
  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：

  4,4'-双甲氧基三苯甲基氯 、 5-氮杂胞苷 以 吡啶 为溶剂， 以2.89 g (59%)的产率得到5'-O-(4,4'-dimethoxytrityl)-5-azacytidine
  参考文献：
  名称：

  5-substituted-2',3'-dideoxycytidine compounds with anti-HTLV-III activity

  摘要：

  抗逆转录病毒活性强的5-取代2',3'-脱氧胞苷化合物及其一磷酸盐已被披露。5-氟和5-氮取代的2',3'-脱氧胞苷化合物已被发现对HTLV-III/LAV病毒有效。

  公开号：

  US04788181A1

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
• 5-substituted-2',3'-dideoxycytidine compounds with anti-HTLV-III activity
  申请人：The United States of America as represented by the Department of Health

  公开号：US04788181A1

  公开（公告）日：1988-11-29

  5-substituted 2',3'-dideoxycytidine compounds and their monophosphates are disclosed which have been found to have potent activity against retroviruses. The 5-fluoro-and 5-aza-substituted 2',3'-dideoycytidine compounds have been found to be effective against HTLV-III/LAV virus.

  抗逆转录病毒活性强的5-取代2',3'-脱氧胞苷化合物及其一磷酸盐已被披露。5-氟和5-氮取代的2',3'-脱氧胞苷化合物已被发现对HTLV-III/LAV病毒有效。
• 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.