8-bromo-2'-deoxy-adenosine 5'-monophosphate | 61286-93-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 8-bromo-2'-deoxy-adenosine 5'-monophosphate
• 英文别名: 8-Bromodeoxyadenosine 5'-monophosphate；[(2R,3S,5R)-5-(6-amino-8-bromopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 61286-93-9
• 化学式: C₁₀H₁₃BrN₅O₆P
• 分子量: 410.121
• InChiKey: QNKYBSSDLXRGGF-KVQBGUIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  8-bromo-2'-deoxy-adenosine 5'-monophosphate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 25.0~55.0 ℃ 、206.84 kPa 条件下， 反应 4.0h， 生成 2'-deoxyguanosine 5'-monophosphate
  参考文献：
  名称：

  Improved Synthesis of 8-Hydroxy-2′-Deoxyadenosine-5′-monophosphate

  摘要：

  Sequential reaction of 2'-deoxyadenosine-5'-monophosphate with bromine, sodium benzyloxide and hydrogen (Pd/C) conveniently gave 8-hydroxy-2'-deoxyadenosine-5'-monophosphate in a 58% overall yield.

  DOI：

  10.1080/00397919308009847
• 作为产物：
  描述：

  2'-脱氧腺苷-5'-单磷酸 在 sodium acetate buffer 、 溴 作用下， 反应 5.0h， 以80%的产率得到8-bromo-2'-deoxy-adenosine 5'-monophosphate
  参考文献：
  名称：

  Improved Synthesis of 8-Hydroxy-2′-Deoxyadenosine-5′-monophosphate

  摘要：

  Sequential reaction of 2'-deoxyadenosine-5'-monophosphate with bromine, sodium benzyloxide and hydrogen (Pd/C) conveniently gave 8-hydroxy-2'-deoxyadenosine-5'-monophosphate in a 58% overall yield.

  DOI：

  10.1080/00397919308009847

文献信息

• OLIGONUCLEOTIDE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20150376611A1

  公开（公告）日：2015-12-31

  The present invention provides an oligonucleotide having improved affinity for AGO2, and the like. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like) or formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like} at the 5′ end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3.

  本发明提供了一种具有改善对AGO2亲和力的寡核苷酸等。该寡核苷酸在其5'端具有由式(I)表示的核苷酸残基或核苷酸残基其中X 1 是氧原子或类似物，R 1 是式(IIA)（其中R 5A 是卤素或类似物，而R 6A 是氢原子或类似物）或式(IVA)（其中Y 3A 是氮原子或类似物，而Y 4A 是CH或类似物），或类似物，R 2 是氢原子、羟基、卤素或可选择地取代的较低烷氧基，而R 3 是氢原子或类似物}，并且该核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• OLIGONUCLEOTIDE HAVING NON-NATURAL NUCLEOTIDE AT 5'-TERMINAL THEREOF
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20170354673A1

  公开（公告）日：2017-12-14

  An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like), formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

  具有由式(I)表示的核苷酸残基或核苷酸残基的寡核苷酸其中X1是氧原子或类似物，R1是式(IIA)（其中R5A是卤素或类似物，而R6A是氢原子或类似物），式(IVA)（其中Y3A是氮原子或类似物，而Y4A是CH或类似物），或类似物，R2是氢原子，羟基，卤素，或可选择地取代的较低烷氧基，而R3是氢原子或类似物，或式(VI)（其中n2为1、2或3）}在其5'端，其中核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• Oligonucleotide having non-natural nucleotide at 5′-terminal thereof
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US10342819B2

  公开（公告）日：2019-07-09

  An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) wherein X1 is an oxygen atom or the like, R1 is formula (IIA) (wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like), formula (IVA) (wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like), or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

  具有由式(I)代表的核苷酸残基或核苷残基的寡核苷酸其中X1是氧原子或类似物，R1是式(IIA)（其中R5A是卤素或类似物，R6A是氢原子或类似物），式(IVA)（其中Y3A是氮原子或类似物，Y4A是CH或类似物），或类似物、R2是氢原子、羟基、卤素或任选取代的低级烷氧基，R3是氢原子或类似物，或式（VI）（其中n2是1、2或3）}在其5′端，其中核苷酸残基或核苷残基通过位置3的氧原子与相邻的核苷酸残基结合。
• Oligonucleotide
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US10378011B2

  公开（公告）日：2019-08-13

  An oligonucleotide having improved affinity for AGO2 is disclosed. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein X1 is an oxygen atom or the like, R1 is formula (IIA), wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like, or formula (IVA) wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like, or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like at the 5′ end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3. A method for improving the knockdown activity of an oligonucleotide wherein the oligonucleotide has a knockdown activity against an mRNA encoding a protein involved in a disease.

  本发明公开了一种对 AGO2 具有更好亲和力的寡核苷酸。该寡核苷酸具有由式（I）代表的核苷酸残基或核苷残基，其中 X1 是氧原子或类似物，R1 是式（IIA），其中 R5A 是卤素或类似物，R6A 是氢原子或类似物，或式（IVA），其中 Y3A 是氮原子或类似物、和 Y4A 是 CH 或类似物，或类似物，R2 是氢原子、羟基、卤素或任选取代的低级烷氧基，R3 是其 5′端的氢原子或类似物，核苷酸残基或核苷残基通过位置 3 的氧原子与相邻的核苷酸残基结合。一种提高寡核苷酸敲除活性的方法，其中寡核苷酸对编码涉及疾病的蛋白质的mRNA具有敲除活性。
• 2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives
  作者：Bo Zhang、Gerd K. Wagner、Karin Weber、Clive Garnham、Anthony J. Morgan、Antony Galione、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm7010386

  日期：2008.3.1

  The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2'-deoxy-cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8-O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5'-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2'-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2'-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2'-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membrane-permeant in whole eggs. Classical antagonists 2 and 3 also showed. previously unobserved agonist activity at higher concentrations in both systems. The 2'-OH group, without effect on the Ca(2+)-mobilizing ability of cADPR itself, is an important motif for the antagonistic activities of 8-substituted cADPR analogues.