9-(3-C-ethynyl-β-D-ribofuranosyl)guanine | 180300-56-5

• 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: 9-(3-C-ethynyl-β-D-ribofuranosyl)guanine
• 英文别名: 2-amino-9-[(2R,3R,4S,5R)-4-ethynyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 180300-56-5
• 化学式: C₁₂H₁₃N₅O₅
• 分子量: 307.266
• InChiKey: YJNWCKUDAMXWKN-OEBFKYMWSA-N

物化性质

• 密度：
  1.89±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  22
• 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：
  155
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-D-ribofuranose 在 吡啶 、 sodium methylate 、 四氯化锡 、 六甲基二硅氮烷 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 9-(3-C-ethynyl-β-D-ribofuranosyl)guanine
  参考文献：
  名称：

  Nucleosides and Nucleotides. 158. 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)- cytosine, 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)uracil, and Their Nucleobase Analogues as New Potential Multifunctional Antitumor Nucleosides with a Broad Spectrum of Activity

  摘要：

  We previously designed 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) as a potential multifunctional antitumor nucleoside antimetabolite. It showed a potent and broad spectrum of antitumor activity against various human tumor cells in vitro and in vivo. To determine the structure-activity relationship, various nucleobase analogues of EUrd, such as 5-fluorouracil, thymine, cytosine, 5-fluorocytosine, adenine, and guanine derivatives, were synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofuranose (6) and the corresponding pertrimethylsilylated nucleobases in the presence of SnCl4 or TIMSOTf as a Lewis acid in CH3CN followed by debenzoylation. The in vitro tumor cell growth inhibitory activity of these 3'-C-ethynyl nucleosides against mouse leukemia L1210 and human nasopharyngeal KB cells showed that 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and EUrd were the most potent inhibitors in the series, with IC50 values for L1210 cells of 0.016 and 0.13 mu M and for KB cells of 0.028 and 0.029 mu M, respectively. 5-Fluorocytosine, 5-fluorouracil, and adenine nucleosides showed much lower activity, with IC50 values of 0.4-2.5 mu M, while thymine and guanine nucleosides did not exhibit any activity up to 300 mu M. We next evaluated the tumor cell growth inhibitory activity of ECyd and EUrd against 36 human tumor cell lines in vitro and found that they were highly effective against these cell lines with IC50 values in the nanomolar to micromolar range. These nucleosides have a similar inhibitory spectrum. The in vivo antitumor activities of ECyd and EUrd were compared to that of 5-fluorouracil against 11 human tumor xenografts including three stomach, three colon, two pancreas, one renal, one breast, and one bile duct cancers. ECyd and EUrd showed a potent tumor inhibition ratio (73-92% inhibition relative to the control) in 9 of 11 and 8 of 11 human tumors, respectively, when administered intravenously for 10 consecutive days at doses of 0.25 and 2.0 mg/kg, respectively, while 5-fluorouracil showed potent inhibitory activity against only one tumor. Such excellent antitumor activity suggests that ECyd and EUrd are worth evaluating further for use in the treatment of human cancers.

  DOI：

  10.1021/jm960537g

文献信息

• Nucleotide mimics and their prodrugs
  申请人：——

  公开号：US20040059104A1

  公开（公告）日：2004-03-25

  The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

  本发明涉及核苷二磷酸模拟物和核苷三磷酸模拟物，其中包含二磷酸或三磷酸基团模拟物，以及可选的糖修饰和/或碱基修饰。本发明的核苷酸模拟物，以药学上可接受的盐、药学上可接受的前药或药物配方的形式，可用作抗病毒、抗微生物和抗癌剂。本发明提供了一种治疗病毒感染、微生物感染和增生性疾病的方法。本发明还涉及包含本发明化合物的药物组合物，可选地与其他药理活性剂结合。
• 3'-SUBSTITUTED NUCLEOSIDE DERIVATIVES
  申请人：TAIHO PHARMACEUTICAL CO., LTD.

  公开号：EP0747389A1

  公开（公告）日：1996-12-11

  The invention relates to a 3'-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3'-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.

  本发明涉及由以下通式（1）代表的 3'-取代的核苷衍生物： 其中 B 表示可具有取代基的核酸碱基，Z 表示可被式中代表的基团取代的低级炔基或低级烯基： 其中，Ra、Rb 和 Rc 分别为低级烷基或苯基，或可具有至少一个低级烷基的环氧乙烷基，R1 和 R2 分别代表 H 或可容易地留在生物体内的酯形成残基，R3 为 H、单磷酸或多磷酸残基或可容易地留在生物体内的酯形成残基，但糖基为核糖或其药学上可接受的盐。根据本发明，3'-取代的核苷衍生物具有优异的抗肿瘤活性，因此可用于治疗和预防癌症。
• Compositions and methods for synthesis of phosphorylated molecules
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US11021497B2

  公开（公告）日：2021-06-01

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.

  本发明提供了合成磷酸化有机化合物（包括核苷三磷酸酯）的组合物和方法。
• Compositions and Methods for Synthesis of Phosphorylated Molecules
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20200239500A1

  公开（公告）日：2020-07-30

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.
• US5763418A
  申请人：——

  公开号：US5763418A

  公开（公告）日：1998-06-09