2'-N,4'-C-[(N-methylamino)oxymethylene]uridine | 1207867-69-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-N,4'-C-[(N-methylamino)oxymethylene]uridine
• 英文别名: 1-[(1R,5S,7R,8S)-8-hydroxy-5-(hydroxymethyl)-2-methyl-3,6-dioxa-2-azabicyclo[3.2.1]octan-7-yl]pyrimidine-2,4-dione
• CAS: 1207867-69-3
• 化学式: C₁₁H₁₅N₃O₆
• 分子量: 285.257
• InChiKey: DQFPUWYQSYUPRO-LOKLDPHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-N,4'-C-[(N-methylamino)oxymethylene]uridine 、 4,4'-双甲氧基三苯甲基氯 在 吡啶 作用下， 反应 8.0h， 以79%的产率得到5'-O-(DMT)-2'-N,4'-C-[(N-methylamino)oxymethylene]uridine
  参考文献：
  名称：

  Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

  摘要：

  To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2'4'-BNA(NC)[NMe], and 2',4'-BNA(NC) bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] modifications showed improved in vivo activity (> 5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

  DOI：

  10.1021/jm9013295
• 作为产物：
  描述：

  1-[(1R,5S,7R,8S)-2-methyl-8-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)-3,6-dioxa-2-azabicyclo[3.2.1]octan-7-yl]pyrimidine-2,4-dione 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以86%的产率得到2'-N,4'-C-[(N-methylamino)oxymethylene]uridine
  参考文献：
  名称：

  Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

  摘要：

  To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2'4'-BNA(NC)[NMe], and 2',4'-BNA(NC) bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] modifications showed improved in vivo activity (> 5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

  DOI：

  10.1021/jm9013295

文献信息

• POLYCYCLIC SUGAR SURROGATE-CONTAINING OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN GENE MODULATION
  申请人：Allerson Charles

  公开号：US20080039618A1

  公开（公告）日：2008-02-14

  Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modification comprising a polycyclic sugar surrogate. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a polycyclic sugar surrogate modification.

  提供了包含第一和第二寡聚物的组合物，其中第一寡聚物的至少一部分能够与第二寡聚物的至少一部分杂交，第一寡聚物的至少一部分与所选目标核酸互补并能够杂交，并且第一或第二寡聚物中至少一个包括具有多环糖代替物的修饰。还提供了寡聚物/蛋白质组合物，其中包括与所选目标核酸互补并能够杂交的寡聚物和至少包括RNA诱导沉默复合物（RISC）的一部分的蛋白质，其中寡聚物的至少一个核苷酸具有多环糖代替物修饰。
• CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND SOUTHERN CONFORMATIONAL GEOMETRY
  申请人：Monia Brett P.

  公开号：US20090258931A1

  公开（公告）日：2009-10-15

  The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3′-endo conformational geometry (3′-endo regions) or DNA like having southern or C2′-endo/O4′-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.

  本发明涉及新型嵌合寡聚物化合物，具有多个交替区域，其具有类似RNA的北方或3'-endo构型几何形状（3'-endo区域）或类似DNA的南方或C2'-endo/O4'-endo构型几何形状。本发明的寡聚物化合物已在多个体外和体内试验系统中显示出mRNA水平的降低，并且可用于调查和治疗目的等方面。
• US7696345B2
  申请人：——

  公开号：US7696345B2

  公开（公告）日：2010-04-13
• US8124745B2
  申请人：——

  公开号：US8124745B2

  公开（公告）日：2012-02-28
• US8791083B2
  申请人：——

  公开号：US8791083B2

  公开（公告）日：2014-07-29