β-(D)-2’,3’-Dideoxy-2’-fluoro-cytidine | 122929-23-1

• 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: β-(D)-2’,3’-Dideoxy-2’-fluoro-cytidine
• 英文别名: Cytidine, 2',3'-dideoxy-2'-fluoro-；4-amino-1-[(2R,3R,5S)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 122929-23-1
• 化学式: C₉H₁₂FN₃O₃
• 分子量: 229.211
• InChiKey: LTDCCBLBAQXNKP-SHYZEUOFSA-N

物化性质

• 熔点：
  234-237 °C (decomp)
• 沸点：
  418.0±55.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(羟基甲基)二氢-2(3H)-呋喃酮 在 4-二甲氨基吡啶 、 氟化铵 、 三氟甲磺酸三甲基硅酯 、 氨 、 二异丁基氢化铝 、 N-氟代双苯磺酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.08h， 生成 β-(D)-2’,3’-Dideoxy-2’-fluoro-cytidine
  参考文献：
  名称：

  A Completely Diastereoselective Electrophilic Fluorination of a Chiral, Noncarbohydrate Sugar Ring Precursor:  Application to the Synthesis of Several Novel 2‘-Fluoronucleosides

  摘要：

  A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been developed. The use of N-fluorodibenzenesulfonimide (5) for the electrophilic fluorination of chiral lactone 4, which is derived from L-glutamic acid, yields the key intermediate 6. This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel alpha-2'-fluoronucleosides. Since glutamic acid is used as the synthetic starting material, the L enantiomer may also be synthesized simply by using D-glutamic acid. The incorporation of fluorine into the 2' position of the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. Further, fluorine is a close mimic of hydroxyl groups in size and polarity and in its ability to act as a hydrogen bond acceptor. This may aid in the recognition of these nucleosides by the enzymes involved in nucleoside activation.

  DOI：

  10.1021/jo9717898

文献信息

• Synthesis and antiviral activity of monofluoro and difluoro analogs of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1)
  作者：Joseph A. Martin、David J. Bushnell、Ian B. Duncan、Stephen J. Dunsdon、Michael J. Hall、Peter J. Machin、John H. Merrett、Kevin E. B. Parkes、Noel A. Roberts

  DOI：10.1021/jm00170a015

  日期：1990.8

  A range of 2'-fluoro and 2',3'-difluoro analogues of pyrimidine deoxyribonucleosides have been synthesized and evaluated against human immunodeficiency virus (HIV-1) in a human lymphoblastoid cell line. Among these compounds, 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12), 2',3'-didehydro-2',3'-dideoxy-2'-fluorocytidine (35), 1-(2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)cytosine

  合成了一系列嘧啶脱氧核糖核苷的2'-氟和2'，3'-二氟类似物，并在人淋巴母细胞样细胞系中针对人免疫缺陷病毒（HIV-1）进行了评估。在这些化合物中，1-（2,3-二脱氧-2-氟-β-D-叔戊基呋喃糖基）胞嘧啶（12），2'，3'-二脱氢-2'，3'-二脱氧-2'-氟胞苷（35） ），1-（2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl）cytosine（41）和3'-deoxy-2'，3'-deidehydro-2'-fluorothymidine（45）为被发现具有显着的抗病毒活性，IC50值分别为0.65、10、10和100 microM。讨论了构效关系。
• NUCLEOSIDE PHOSPHONATE DERIVATIVES
  申请人：Or Yat Sun

  公开号：US20090274686A1

  公开（公告）日：2009-11-05

  The present invention discloses compounds of formula (I) or (II), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.

  本发明揭示了化合物的公式(I)或(II)，或其药学上可接受的盐、酯或前药：这些化合物抑制、预防或治疗异常细胞增殖和/或病毒感染，特别是HIV、HCV或HBV。因此，本发明的化合物干扰病毒的复制周期，同时也可用作抗病毒剂，或干扰宿主细胞的生化过程，同时也可用作抗增殖剂。本发明还涉及包含上述化合物的药物组合物，用于治疗患有病毒感染和/或细胞增殖的受试者。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的病毒感染和/或细胞增殖的方法。本发明涉及上述新型抗病毒/抗增殖化合物，包括含有这些化合物的药物组合物，以及用于治疗或预防受试者的病毒感染的方法。
• Nuclease resistant chimeric oligonucleotides
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20030158403A1

  公开（公告）日：2003-08-21

  The present invention relates to novel nuclease-resistant oligomeric compounds and to novel methods for increasing the nuclease resistance of oligomeric compounds. In preferred embodiments of the invention, the oligomeric compounds comprise at least one modified nucleoside containing a modified sugar moiety at either the 3′ or 5′ terminus of the oligomeric compound, and further comprise at least one internucleoside linking group that is other than phosphodiester. Other preferred embodiments of the invention include methods of enhancing the nuclease resistance of oligomeric compounds comprising incorporating at least one modified nucleoside containing a modified sugar moiety at either the 3′ or 5′ terminus of an oligomeric compound.

  本发明涉及新型核酸酶抗性寡聚合物化合物以及增加寡聚合物化合物核酸酶抗性的新方法。在本发明的优选实施例中，寡聚合物化合物包括至少一个含有修饰糖基团的修饰核苷酸，该修饰核苷酸位于寡聚合物化合物的3'端或5'端，而且还包括至少一个不是磷酸二酯的核苷酸之间连接的核苷酸连接基团。本发明的其他优选实施例包括增强寡聚合物化合物核酸酶抗性的方法，其中包括将至少一个含有修饰糖基团的修饰核苷酸合并到寡聚合物化合物的3'端或5'端。
• 2'-fluoronucleosides
  申请人：——

  公开号：US20020198171A1

  公开（公告）日：2002-12-26

  A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: 1 wherein Base is a purine or pyrimidine base; R 1 is OH, H, OR 3 , N 3 , CN, halogen, including F, or CF 3 , lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R 2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R 2 is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R 3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.

  本发明揭示了一类2'-氟核苷类化合物，其可用于治疗乙型肝炎感染、丙型肝炎感染、艾滋病毒和异常细胞增殖，包括肿瘤和癌症。该化合物具有以下通式： 其中，基团表示嘌呤或嘧啶碱基；R1为OH、H、OR3、N3、CN、卤素（包括F）或CF3、低烷基、氨基、低烷基氨基、二（低）烷基氨基或烷氧基，基团表示嘌呤或嘧啶碱基；R2为H、磷酸酯（包括一磷酸盐、二磷酸盐、三磷酸盐或稳定的磷酸酯前药）、酰基或其他在体内可提供R2为H或磷酸酯的药学上可接受的离去基团；磺酸酯包括烷基或芳基烷基磺酰基，包括甲烷磺酰基、苄基，其中苯基基团可选择地被一个或多个如上所述的取代基所取代，脂质、氨基酸、肽或胆固醇；以及R3为酰基、烷基、磷酸酯或其他在体内可裂解为母体化合物的药学上可接受的离去基团，或其药学上可接受的盐。
• 2'-Fluoronucleosides
  申请人：——

  公开号：US20040254141A1

  公开（公告）日：2004-12-16

  A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: 1 wherein Base is a purine or pyrimidine base; R 1 is OH, H, OR 3 , N 3 , CN, halogen, including F, or CF 3 , lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R 2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R 2 is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R 3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.

  本发明涉及一类2'-氟核苷化合物，其在治疗乙型肝炎感染、丙型肝炎感染、HIV和异常细胞增殖，包括肿瘤和癌症方面有用。该化合物具有以下通用式：1其中Base是嘌呤或嘧啶碱基；R1是OH、H、OR3、N3、CN、卤素，包括F或CF3、低烷基、氨基、低烷基氨基、二（低）烷基氨基或烷氧基，且base是指嘌呤或嘧啶碱基；R2是H、磷酸，包括一磷酸盐、二磷酸盐、三磷酸盐或稳定的磷酸盐前药；酰基或其他在体内可以提供R2为H或磷酸的药学上可接受的离去基；磺酸酯，包括烷基或芳基烷基磺酰，包括甲烷磺酰、苯甲基，其中苯基可以选择性地用上述芳基定义中描述的一个或多个取代基置换；脂质、氨基酸、肽或胆固醇；以及R3是酰基、烷基、磷酸盐或其他在体内可以裂解为母化合物的药学上可接受的离去基，或其药学上可接受的盐。