EUrd | 180300-49-6

• 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: EUrd
• 英文别名: 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil；1-(3-C-ethynyl-β-D-ribofuranosyl)uracil；1-(3-C-Ethynylribopentofuranosyl)uracil；1-[(2R,3R,4S,5R)-4-ethynyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 180300-49-6
• 化学式: C₁₁H₁₂N₂O₆
• 分子量: 268.226
• InChiKey: KNGMLOFYXFWJLZ-DYUFWOLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  EUrd 在 吡啶 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 1-[3-C-ethynyl-2-O-[phenoxy(thiocarbonyl)]-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-ribo-pentofuranosyl]uracil
  参考文献：
  名称：

  乙炔基铈试剂的非对映选择性加成和Barton-McCombie反应是合成C-3'-乙炔基核糖核苷和C-3'-乙炔基-2'-脱氧核糖核苷的关键步骤。

  摘要：

  我们描述了从相应的核苷开始制备3'-炔基尿苷4a和-腺苷4b以及3'-炔基-2'-脱氧尿苷16a和-腺苷16b的方法。通过使乙炔基铈-锂试剂在3'-酮核苷上与未保护的C-5'处的羟基反应，可获得所需的C-3'叔醇立体化学。通过Barton-McCombie反应在适当的条件下进行2'-脱氧，其中在三键上抑制了氢化锡的添加。报道了对C-3'修饰的核苷的抗HIV活性的评估。

  DOI：

  10.1021/jo9704568
• 作为产物：
  描述：

  1-(2,3,5-tri-O-benzoyl-3-C-ethynyl-β-D-ribofuranosyl)uracil 在 氨 作用下， 以 甲醇 为溶剂， 以85%的产率得到EUrd
  参考文献：
  名称：

  Nucleosides and nucleotides. 152. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside

  摘要：

  1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2'-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost ail the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00339-3

文献信息

• [EN] COMPOSITIONS AND METHODS FOR SYNTHESIS OF PHOSPHORYLATED MOLECULES<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULES PHOSPHORYLÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195494A1

  公开（公告）日：2019-10-10

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

  这项发明提供了合成磷酸化有机化合物的组合物和方法，包括核苷三磷酸。
• 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。
• SYNTHESIS OF ARA-2'-O-METHYL-NUCLEOSIDES, CORRESPONDING PHOSPHORAMIDITES AND OLIGONUCLEOTIDES INCORPORATING NOVEL MODIFICATIONS FOR BIOLOGICAL APPLICATION IN THERAPEUCTICS, DIAGNOSTICS, G- TETRAD FORMING OLIGONUCLEOTIDES AND APTAMERS
  申请人：Srivastava Suresh C.

  公开号：US20120149888A1

  公开（公告）日：2012-06-14

  The present invention relates to synthesis, purification and methods to obtain high purity novel 2′-arabino-O-methyl nucleosides and the corresponding phosphoramidites of various arabinonucleoside bases and introduction of such units into defined sequence synthetic DNA and RNA. Various synthetic oligonucleotides, such as HIV integrase inhibitor 14-mer and thrombin binding oligonucleotide, thrombin-1, bearing ara-2′-omethyl modification have been synthesized. It is anticipated the oligonucleotides incorporating these monomers will exhibit biological activities related to antisense approach approach, design of better SiRNA's, diagnostic agents. Similarly, it is anticipated that oligonucleotides incorporating such novel nucleosides will be useful to develop therapeutic candidates designing stable G-quadruplexes and Aptamers for oligonucleotide structure, folding topology, evaluation of biochemical properties and design and develop as therapeutic agents. It is further anticipated that the nucleosides, phosphates and triphosphates of this invention could develop as therapeutic agents.

  本发明涉及合成、纯化和获取高纯度新型2'-阿拉伯核苷-O-甲基核苷和各种阿拉伯核苷基的相应磷酰胺酯的方法，并将这些单元引入到定义的序列合成DNA和RNA中。已合成了各种合成寡核苷酸，例如HIV整合酶抑制剂14-mer和凝血酶结合寡核苷酸，凝血酶-1，带有ara-2'-omethyl修饰。预计包含这些单体的寡核苷酸将展示与反义方法、更好的SiRNA设计、诊断剂相关的生物学活性。同样，预计包含这些新型核苷的寡核苷酸将有助于开发稳定的G四链体和寡核苷酸结构的Aptamers，用于寡核苷酸结构、折叠拓扑、生化特性的评估和设计和开发为治疗剂。进一步预计，本发明的核苷、磷酸盐和三磷酸盐可作为治疗剂开发。
• 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。
• D-PENTOFURANOSE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP0842942A1

  公开（公告）日：1998-05-20

  The present invention relates to D-pentofuranose derivatives represented by the following formulas (1) through (4): (wherein A represents a chlorobenzoyl group; R1 represents a hydrogen atom, an aliphatic lower acyl group, a substituted or unsubstituted benzoyl group; each of X and Y represents a lower alkyl group; Z represents an ethynyl group or tri-lower alkyl silylethynyl group; the sugar moiety in formula (1) represents xylose; and the sugar moiety of each of formulas (3) and (4) represents ribose). The present invention also relates to a process for preparing the compound (2) characterized by oxidizing the compound of formula (1) with a hypochlorite in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidinoxy compound. These compounds are useful as intermediates in the synthesis of 3'-C-substituted ribonucleoside derivatives having excellent antitumor activities.

  本发明涉及由下式(1)至(4)代表的D-戊呋喃糖衍生物： (其中A代表氯代苯甲酰基；R1代表氢原子、脂肪族低级酰基、取代或未取代的苯甲酰基；X和Y各自代表低级烷基；Z代表乙炔基或三低级烷基硅烷基乙炔基；式(1)中的糖基代表木糖；式(3)和(4)各自的糖基代表核糖)。本发明还涉及一种制备化合物（2）的工艺，其特征是在催化量的 2，2，6，6-四甲基哌啶氧基化合物存在下，用次氯酸盐氧化式（1）化合物。 这些化合物可作为合成 3'-C 取代的核糖核苷衍生物的中间体，具有优异的抗肿瘤活性。