5-(pyridin-2-yl)-2'-deoxyuridine

• 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: 5-(pyridin-2-yl)-2'-deoxyuridine
• 英文别名: 5-(2-pyridinyl)-2'-deoxyuridine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-pyridin-2-ylpyrimidine-2,4-dione
• 化学式: C₁₄H₁₅N₃O₅
• 分子量: 305.29
• InChiKey: RAOLYRCIRSJZJN-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  碘苷 、 2-(三甲基甲锡烷基)吡啶 在 双三苯基磷二氯化钯 silica gel 、 甲醇 、 二氯甲烷 、 氨 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以to yield 0.253 g (83%) of the title compound as a white solid m.p. 201-203° C.的产率得到5-(pyridin-2-yl)-2'-deoxyuridine
  参考文献：
  名称：

  Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines

  摘要：

  本发明揭示了一种新型寡聚物，与仅含传统碱基的寡聚物相比，其形成双链或三链的能力得到了增强。这些寡聚物含有5-（1-丙炔基）尿嘧啶，5-（1-丙炔基）胞嘧啶或相关类似物。本发明的寡聚物能够（i）通过在生理pH下耦合到靶DNA双链的主沟槽中，与各种靶序列（如病毒或癌基因序列）形成三链，或（ii）通过结合单链DNA或靶基因编码的RNA而形成双链。本发明的寡聚物可以被纳入药学可接受载体中，并可以构建任何所需的序列，只要序列通常包括一种或多种用本发明的类似物替换的碱基。本发明的组合物可以用作治疗各种病毒引起的疾病的药物，也可以用于诊断目的，以检测病毒或疾病情况。

  公开号：

  US06380368B1

文献信息

• Enhanced triple-helix and double-helix formation with oligomers
  申请人：Gilead Sciences, Inc.

  公开号：US05645985A1

  公开（公告）日：1997-07-08

  Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used used for diagnostic purposes in order to detect viruses or disease conditions.

  揭示了一种新型寡聚体，相对于仅含有传统碱基的寡聚体，具有更强的形成双链或三链的能力。这些寡聚体包含碱基5-(1-丙炔基)尿嘧啶，5-(1-丙炔基)胞嘧啶或相关类似物。本发明的寡聚体能够（i）与各种目标序列如病毒或癌基因序列形成三链，通过在生理pH下耦合到目标DNA双链的主沟；或者（ii）通过结合到单链DNA或由目标基因编码的RNA而形成双链。本发明的寡聚体可以构建成具有任何所需序列，只要该序列通常包括一个或多个被本发明类似物替代的碱基。本发明的组合物可用于诊断目的，以便检测病毒或疾病情况。
• ENHANCED TRIPLE-HELIX AND DOUBLE-HELIX FORMATION WITH OLIGOMERS CONTAINING MODIFIED PYRIMIDINES
  申请人：——

  公开号：US20040265802A9

  公开（公告）日：2004-12-30

  Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

  本发明披露了一种新型寡聚物，与仅含传统碱基的寡聚物相比，其具有增强的双链或三链形成能力。该寡聚物包含碱基5-(1-丙炔基)尿嘧啶，5-(1-丙炔基)胞嘧啶或相关类似物。本发明的寡聚物能够(i)在生理pH下通过耦合到目标DNA双链的主沟槽形成三链，如病毒或癌基因序列，或(ii)通过结合到单链DNA或由目标基因编码的RNA形成双链。本发明的寡聚物可以被纳入到药学可接受的载体中，并且可以构建任何所需的序列，只要该序列通常包括一个或多个被本发明的类似物替换的碱基。本发明的组合物可以用作制药剂治疗各种疾病，如由病毒引起的疾病，并且可以用于诊断目的，以检测病毒或疾病情况。
• Methods of using oligomers containing modified pyrimidines
  申请人：Gilead Sciences, Inc.

  公开号：US05830653A1

  公开（公告）日：1998-11-03

  Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. compositions of the invention can be used as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

  本发明揭示了一种新型寡聚物（oligomers），与仅含有传统碱基的寡聚物相比，该寡聚物具有更强的形成双链或三链结构的能力。该寡聚物包含碱基5-（1-丙炔基）尿嘧啶，5-（1-丙炔基）胞嘧啶或相关类似物。本发明的寡聚物能够（i）通过在生理pH下耦合到靶DNA双链的主沟槽中，与各种靶序列（如病毒或癌基因序列）形成三链结构；或者（ii）通过结合到单链DNA或由靶基因编码的RNA来形成双链结构。本发明的寡聚物可以被纳入到药学可接受的载体中，并且可以构建任何所需的序列，只要该序列通常包含一个或多个被本发明的类似物替换的碱基。本发明的组合物可以用作制药剂治疗各种疾病，例如由病毒引起的疾病，并且可以用于诊断目的，以检测病毒或疾病情况。
• Oligomers containing modified pyrimidines
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP1256589A2

  公开（公告）日：2002-11-13

  An oligomer comprising at least two nucleomonomers and pharmaceutically acceptable salts thereof wherein at least one of said nucleomonomers comprises a base of formula (1) or (2): wherein each X is independently O or S; R2 is a group comprising at least one pi bond connected to the carbon atom attached to the base; Pr is (H)2 or a protecting group;    with the proviso that when at least one of said nucleomonomers of said oligomer comprises deoxyuridine 5-substituted by vinyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1-propynyl, 1-butynyl, 1-hexynyl, 1-heptynyl, or 1-octynyl, then the remainder of the nucleomonomers comprising said oligomer are not solely comprised of phosphodiester linked 2'-deoxyadenosine, 2'deoxyguanosine, 2'-deoxycytidine, thymidine or a combination thereof; and wherein said oligomer includes at least one unit having one of thirteen specific formulas.

  由至少两种核单体及其药学上可接受的盐组成的低聚物，其中至少一种核单体包括式 (1) 或 (2) 的碱： 其中每个 X 独立地为 O 或 S； R2 是一个基团，包含至少一个与连接到碱的碳原子相连的π键； Pr 是 (H)2 或保护基团； 1-庚炔基、1-庚炔基、1-辛炔基、1-丙炔基、1-丁炔基、1-己炔基、1-庚炔基或 1-辛炔基，则组成所述低聚物的核单体的其余部分并非仅由磷酸二酯连接的 2'-脱氧腺苷、2'-脱氧鸟苷、2'-脱氧胞苷、胸腺嘧啶或其组合组成；其中所述低聚物包括至少一个具有十三种特定公式之一的单元。
• 5-Heteroaryl-2'-deoxyuridine Analogs. Synthesis and Incorporation into High-Affinity Oligonucleotides
  作者：Arnold J. Gutierrez、Terry J. Terhorst、Mark D. Matteucci、Brian C. Froehler

  DOI：10.1021/ja00092a003

  日期：1994.6

  A series of C-5 heteroaryl-2'-deoxyuridines were synthesized from 5-iodo-2'-deoxyuridine. Palladium catalyzed coupling with heteroarylstannanes proved to be a convenient and general method of preparation. Oligonucleotides containing pyridine-, thiophene-, thiazole-, and imidazole-substituted 2'-deoxyuridine analogs gave enhanced thermal stability to complementary RNA relative to thymidine. Thermal denaturation studies showed that oligodeoxynucleotides (ODNs) containing 5-(thiazol-2-yl)-2'-deoxyuridine exhibit the highest thermal denaturation (Tm) and therefore may increase the potency of these ODNs to inhibit gene expression in a sequence specific manner.