4'-ethynyl-2'-deoxyribofuranosyl-2,6-diaminopurine | 306305-12-4

• 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: 4'-ethynyl-2'-deoxyribofuranosyl-2,6-diaminopurine
• 英文别名: 9-(2-deoxy-4-C-ethynyl-ribo-pentofuranosyl)-2,6-diaminopurine；9-(2-deoxy-4-C-ethynyl-β-D-ribo-pentofuranosyl)-2,6-diaminopurine；9-(4-C-ethynyl-2-deoxy-β-D-ribo-furanosyl)-2,6-diaminopurine；Adenosine, 2-amino-2'-deoxy-4'-C-ethynyl-；(2R,3S,5R)-5-(2,6-diaminopurin-9-yl)-2-ethynyl-2-(hydroxymethyl)oxolan-3-ol
• CAS: 306305-12-4
• 化学式: C₁₂H₁₄N₆O₃
• 分子量: 290.282
• InChiKey: XDHLSXXFUCIEFB-QRPMWFLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4'-ethynyl-2'-deoxyribofuranosyl-2,6-diaminopurine 在 Tris-HCl buffer 、 adenosine deaminase 作用下， 反应 2.0h， 以50%的产率得到4'-ethynyl-2'-deoxyguanosine
  参考文献：
  名称：

  Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity

  摘要：

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

  DOI：

  10.1021/jm000209n
• 作为产物：
  描述：

  2,6-二氨基嘌呤-2'-脱氧核苷 在 吡啶 、 咪唑 、 sodium hydroxide 、 sodium tetrahydroborate 、 三甲基氯硅烷 、 potassium tert-butylate 、 四丁基氟化铵 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 甲胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 氯仿 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 18.58h， 生成 4'-ethynyl-2'-deoxyribofuranosyl-2,6-diaminopurine
  参考文献：
  名称：

  4'-C-氰基-和4'-C-乙炔基-2'-脱氧嘌呤核苷的设计，高效合成和抗HIV活性。

  摘要：

  一些4'-C-乙炔基-2'-脱氧嘌呤核苷在一系列4'-C-取代的2'-脱氧核苷中显示出最有效的抗HIV活性，其4'-C取代基为甲基，乙基，乙炔基和以此类推。我们的假设是，它们在C-4'位的取代基越小，它们显示出的生物活性就越好。因此，取代基小于乙炔基的4'-C-氰基-2'-脱氧嘌呤核苷将具有更强的抗病毒活性。为了证明我们的假设，我们计划开发4'-C-氰基-2'-脱氧嘌呤核苷（4'-CNdNs）和4'-C-乙炔基-2'-脱氧嘌呤核苷（4'- EdNs）。因此，我们成功开发了六个2'的有效合成 -在2'-脱氧腺苷和2,6-二氨基嘌呤2'-脱氧核糖苷的糖部分的C-4'位置带有氰基或乙炔基的-脱氧嘌呤核苷。不幸的是，4'-C-氰基衍生物显示出较低的抗HIV-1活性，而两种4'-C-乙炔基衍生物表明其体内毒性很高。

  DOI：

  10.1081/ncn-120037508

文献信息

• [EN] 4'-C-ETHYNYL PURINE NUCLEOSIDES<br/>[FR] NUCLEOSIDES DE PURINE 4'-C-ETHYNYLE
  申请人：YAMASA CORP

  公开号：WO2000069877A1

  公开（公告）日：2000-11-23

  The invention provides 4'-C-ethynyl purine nucleosides represented by formula (I), wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  该发明提供了由式(I)表示的4'-C-乙炔基嘌呤核苷，其中B代表从嘌呤及其衍生物组成的群体中选择的碱基；X代表氢原子或羟基；而R代表氢原子或磷酸盐残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。最好，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4'-C-ethynyl pyrimidine nucleoside compounds
  申请人：——

  公开号：US20020022722A1

  公开（公告）日：2002-02-21

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: 1 wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  本发明提供了4'-C-乙炔基嘧啶核苷（不包括4'-C-乙炔基胸腺嘧啶）的化合物，其化学式为[I]：其中B代表从嘧啶和其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有上述任一化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4′-C-ethynyl pyrimidine nucleosides and pharmaceutical compositions thereof
  申请人：Yamasa Corporation

  公开号：US06403568B1

  公开（公告）日：2002-06-11

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  本发明提供了4'-C-乙炔基嘧啶核苷（不包括4'-C-乙炔基胸腺嘧啶）的化合物，其化学式表示为[I]：其中B代表从嘧啶和其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4′-C-ethynyl pyrimidine nucleoside compounds and pharmaceutical compositions
  申请人：Yamasa Corporation

  公开号：US06291670B1

  公开（公告）日：2001-09-18

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  本发明提供了4'-C-乙炔基嘧啶核苷类化合物（不包括4'-C-乙炔基胸腺嘧啶），其化学式为[I]：其中B代表从嘧啶及其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸酯基；以及含有任何一种上述化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4′-C-ethynyl purine nucleoside compounds
  申请人：Yamasa Corporation

  公开号：US06333315B1

  公开（公告）日：2001-12-25

  The invention provides 4′-C-ethynyl purine nucleosides represented by formula [I]: wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  该发明提供了由公式[I]所表示的4'-C-乙炔基嘌呤核苷，其中B代表从嘌呤及其衍生物组成的基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。