4-{[(dimethylamino)ethylidene]amino}-3-iodo-1-(5'-O-(4,4'-dimethoxytriphenylmethyl)-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine | 1185880-43-6

• 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: 4-{[(dimethylamino)ethylidene]amino}-3-iodo-1-(5'-O-(4,4'-dimethoxytriphenylmethyl)-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine
• CAS: 1185880-43-6
• 化学式: C₃₅H₃₇IN₆O₆
• 分子量: 764.62
• InChiKey: ZDLJHIMSHDOPHF-WIFIACMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  48.0
• 可旋转键数：
  10.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  136.58
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  4-{[(dimethylamino)ethylidene]amino}-3-iodo-1-(5'-O-(4,4'-dimethoxytriphenylmethyl)-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine 在 copper(l) iodide 、 四(三苯基膦)钯 、 silver nitrate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 4-{[(dimethylamino)ethylidene]amino}-3-[N'-(2-propynyl)-2",2",2"-trifluoroacetamido]-1-(β-D-ribofuranosyl)-5'-O-(4,4'-dimethoxytriphenylmethyl)-3'-O-[(2-cyanoethyl)(N,N-diisopropylamino)phosphino]-2'-O-(tert-butyldimethylsilyl)-1H-pyrazolo-[3,4-d]pyrimidine
  参考文献：
  名称：

  7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove

  摘要：

  在这里，我们描述了新的 7 取代 8-aza-7-deazaadenosine 核糖核苷磷酸酰胺的合成及其在生成主沟修饰双链 RNA 中的应用。通过自动 RNA 合成后的叠氮-炔环加成反应，7-乙炔基类似物使 RNA 的结构进一步多样化。此外，我们还报告了八种不同的嘌呤 7 位修饰对 RNA 双链稳定性和配对特异性影响的初步研究。最后，我们还探讨了 siRNA 引导链中 8 个不同位置的此类修饰对 RNAi 活性的影响。研究发现，具有大的 7 位取代基的类似物能保持腺苷配对特异性，并在 siRNA 引导链的特定位置具有良好的耐受性。

  DOI：

  10.1039/c2ob25647a
• 作为产物：
  描述：

  4-{[(dimethylamino)ethylidene]amino}-3-iodo-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine 、 4,4'-双甲氧基三苯甲基氯 在 吡啶 、 silver nitrate 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以70%的产率得到4-{[(dimethylamino)ethylidene]amino}-3-iodo-1-(5'-O-(4,4'-dimethoxytriphenylmethyl)-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Matching Active Site and Substrate Structures for an RNA Editing Reaction

  摘要：

  The RNA-editing adenosine deaminases (ADARs) catalyze deamination of adenosine to inosine in a double-stranded structure found in various RNA substrates, including mRNAs. Here we present recent efforts to define structure/activity relationships for the ADAR reaction. We describe the synthesis of new phosphoramidites for the incorporation of 7-substituted-8-aza-7-deazaadenosine derivatives into RNA. These reagents were used to introduce the analogues into mimics of the R/G-editing site found in the pre-mRNA for the human glutamate receptor B subunit (GluR B). Analysis of the kinetics of the ADAR2 reaction with analogue-containing RNAs indicated 8-aza-7-deazaadenosine is an excellent substrate for this enzyme with a deamination rate eight times greater than that for adenosine. However, replacing the C7 hydrogen in this analogue with bromine, iodine, or propargyl alcohol failed to increase the deamination rate further but rather decreased the rate. Modeling of nucleotide binding in the enzyme active site suggested amino acid residues that may be involved in nucleotide recognition. We carried out a functional screen of a library of ADAR2 mutants expressed in S. cerevisiae that varied the identity of these residues to identify active deaminases with altered active sites. One of these mutants (ADAR2 R455A) was able to substantially overcome the inhibitory effect of the bulky C7 substituents (-Br, -I, propargyl alcohol). These results advance our understanding of the importance of functional groups found in the edited nucleotide and the role of specific active site residues of ADAR2.

  DOI：

  10.1021/ja9034076