(E)-N-(6-amino-hexyl)-3-[1-((4S,5R)-5-{[bis(4-methoxyphenyl)(phenyl)methoxy]methyl}-4-hydroxy-tetrahydro-2-furanyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (E)-N-(6-amino-hexyl)-3-[1-((4S,5R)-5-{[bis(4-methoxyphenyl)(phenyl)methoxy]methyl}-4-hydroxy-tetrahydro-2-furanyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenamide
• 英文别名: 5-[N-(6-Aminohexyl)-3-E-acrylamido]-2'-deoxy-5'-O-DMT-uridine；(E)-N-(6-aminohexyl)-3-[1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-2,4-dioxopyrimidin-5-yl]prop-2-enamide
• 化学式: C₃₉H₄₆N₄O₈
• 分子量: 698.816
• InChiKey: LZRVIYIHUBJELH-JFYNCNQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  51
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (E)-N-(6-amino-hexyl)-3-[1-((4S,5R)-5-{[bis(4-methoxyphenyl)(phenyl)methoxy]methyl}-4-hydroxy-tetrahydro-2-furanyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 2-{[bis(4-methoxyphenyl)(phenyl)methoxy]methyl}-5-[5-((1E)-3-{[6-(9H-carbazol-2-yloxy)hexyl]amino}-3-oxoprop-1-enyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]tetrahydrofuran-3-yl 2-cyanoethyl diisopropylamidophosphite
  参考文献：
  名称：

  Synthesis of hapten–phosphoramidites from 2′-deoxyuridine

  摘要：

  A total of 11 novel phosphoramidites, 3a-d, 4a-d and 14a-c were prepared from 2'-deoxyuridine functionalized at 5 and 6-position of the pyrimidine ring with hapten reporter groups, e.g. adamantane, carbazole, dansyl and dabsyl, suitable for use in immunodetection nucleic acid testing assays. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)00875-5
• 作为产物：
  描述：

  (E)-3-(1-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-N-(6-(2,2,2-trifluoroacetamido)hexyl)acrylamide 在 ammonium hydroxide 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 42.0h， 以100%的产率得到(E)-N-(6-amino-hexyl)-3-[1-((4S,5R)-5-{[bis(4-methoxyphenyl)(phenyl)methoxy]methyl}-4-hydroxy-tetrahydro-2-furanyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenamide
  参考文献：
  名称：

  [EN] LIGAND-MODIFIED DOUBLE-STRANDED NUCLEIC ACIDS
  [FR] ACIDES NUCLÉIQUES DOUBLE BRIN MODIFIÉS PAR UN LIGAND

  摘要：

  该发明提供了包括具有感链或反义链的5'延伸以及进一步包括与配体结合的多个核苷酸的双链核酸分子，以及使用这些双链核酸分子的方法。其中，感链形成四环的配体修饰寡聚物提供了新的强效和稳定的RNA干扰剂。这些双链核酸分子是使用包括配体修饰单体、核苷酸类似物单体、修饰核苷酸单体等的多个核苷酸合成的，使用标准的核苷酸合成方法和系统。

  公开号：

  WO2016100401A1

文献信息

• Oligonucleotides comprising a non-phosphate backbone linkage
  申请人：Manoharan Muthiah

  公开号：US20060287260A1

  公开（公告）日：2006-12-21

  One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

  本发明的一个方面涉及在3'-位置用磷酰胺基团取代的核糖核苷。在某些实施例中，磷酰胺基团是烷基磷酰胺基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的双链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，非磷酸酯连接仅出现在一条链中。在某些实施例中，非磷酸酯连接出现在两条链中。在某些实施例中，配体结合到包含双链寡核苷酸的寡核苷酸链中的一条链上。在某些实施例中，配体结合到包含双链寡核苷酸的寡核苷酸链中的两条链上。在某些实施例中，寡核苷酸链包含至少一个修饰的糖基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的单链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，配体结合到寡核苷酸链上。在某些实施例中，寡核苷酸包含至少一个修饰的糖基团。
• Oligonucleotides comprising a C5-modified pyrimidine
  申请人：Manoharan Muthiah

  公开号：US20050288244A1

  公开（公告）日：2005-12-29

  One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand. In certain embodiments, a ligand is bound to only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, both of the oligonucleotide strands of the double-stranded oligonucleotide independently comprise a bound ligand. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. In certain embodiments, a phosphate linkage in one or both of the strands of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety. In certain embodiments, a phosphate linkage of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. The ligand improves the pharmacokinetic properties of the oligonucleotide.

  本发明的一个方面涉及包含至少一个配体的双链寡核苷酸。在某些实施例中，配体仅结合到构成双链寡核苷酸的两个核苷酸链中的一个。在某些实施例中，双链寡核苷酸的两个核苷酸链都独立地包含一个结合的配体。在某些实施例中，核苷酸链包含至少一个修饰的糖基。在某些实施例中，核苷酸链的一个或两个链中的磷酸酯键已被磷硫酸酯或磷二硫酸酯键替代。在一个首选实施例中，配体是胆固醇或5β-胆烷酸。本发明的另一个方面涉及包含至少一个配体的单链寡核苷酸。在某些实施例中，核苷酸包含至少一个修饰的糖基。在某些实施例中，核苷酸的磷酸酯键已被磷硫酸酯或磷二硫酸酯键替代。在一个首选实施例中，配体是胆固醇或5β-胆烷酸。配体改善了寡核苷酸的药代动力学性能。
• METHOXATIN DERIVATIVES
  申请人：Hodges John C.

  公开号：US20110152526A1

  公开（公告）日：2011-06-23

  The present invention provides for compounds of Formula I and II: wherein y, X, Y, Z, R 1 , and R 2 have any of the values defined there for in the specification. The compounds of formula I are useful as reagents in the isolation and the assay of PQQ dependent enzymes. Also provided are compositions comprising compounds of Formula I and II.

  本发明提供了化合物的公式I和II：其中y、X、Y、Z、R1和R2具有规范中定义的任何值。公式I的化合物可用作在PQQ依赖酶的分离和测定中的试剂。还提供了包含公式I和II化合物的组合物。
• [EN] LIGAND-MODIFIED DOUBLE-STRANDED NUCLEIC ACIDS<br/>[FR] ACIDES NUCLÉIQUES DOUBLE BRIN MODIFIÉS PAR UN LIGAND
  申请人：DICERNA PHARMACEUTICALS INC

  公开号：WO2016100401A1

  公开（公告）日：2016-06-23

  The invention provides for double stranded nucleic acid molecules comprising a 5 'extension of the sense or antisense strand and further comprising a plurality of nucleotides that are conjugated to a ligand and methods of using the double-stranded nucleic acid molecules. Ligand-modified oligomers where the sense stands form a tetraloop provide new potent and stable RNA interference agents. These dsNA molecules are synthesized using a plurality of nucleotides that include ligand-modified monomers, nucleotide analog monomers, modified nucleotide monomers and the like, using standard nucleotide synthetic methods and systems.

  该发明提供了包括具有感链或反义链的5'延伸以及进一步包括与配体结合的多个核苷酸的双链核酸分子，以及使用这些双链核酸分子的方法。其中，感链形成四环的配体修饰寡聚物提供了新的强效和稳定的RNA干扰剂。这些双链核酸分子是使用包括配体修饰单体、核苷酸类似物单体、修饰核苷酸单体等的多个核苷酸合成的，使用标准的核苷酸合成方法和系统。
• Synthesis of hapten–phosphoramidites from 2′-deoxyuridine
  作者：Maciej Adamczyk、Srinivasa Rao Akireddy、Phillip G Mattingly、Rajarathnam E Reddy

  DOI：10.1016/s0040-4020(03)00875-5

  日期：2003.7

  A total of 11 novel phosphoramidites, 3a-d, 4a-d and 14a-c were prepared from 2'-deoxyuridine functionalized at 5 and 6-position of the pyrimidine ring with hapten reporter groups, e.g. adamantane, carbazole, dansyl and dabsyl, suitable for use in immunodetection nucleic acid testing assays. (C) 2003 Elsevier Science Ltd. All rights reserved.