O6-Substituted Guanine Deriv. 10

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: O6-Substituted Guanine Deriv. 10
• 英文别名: 6-(2-methylbutoxy)-7H-purin-2-amine
• 化学式: C₁₀H₁₅N₅O
• 分子量: 221.262
• InChiKey: OSJJTHVHMYERMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O6-Substituted Guanine Deriv. 10 在 溴 、 sodium acetate 、 溶剂黄146 作用下， 以70%的产率得到
  参考文献：
  名称：

  固相DNA寡聚化的配有互补碱基的亚磷酰胺单体的合成。

  摘要：

  我们描述了两个单体的制备，该单体在边缘带有互补的碱基（鸟嘌呤2'-脱氧胞苷和2-氨基腺嘌呤-2'-脱氧尿苷），并且可以方便地保护和活化以进行固相自动DNA合成。我们报告了优化的合成途径，导致涉及的四个核碱基衍生物，它们交叉偶联反应成含二核碱基的单体，以及它们在DNA合成仪中的低聚。

  DOI：

  10.1021/acs.orglett.9b03801
• 作为产物：
  描述：

  2-氨基-6-氯嘌呤 、 iso-NaOC5H11 以 四氢呋喃 为溶剂， 以71%的产率得到O6-Substituted Guanine Deriv. 10
  参考文献：
  名称：

  Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O⁶-Substituted Guanine Derivatives

  摘要：

  O-6-Substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B I and CDK2/cyclin A, the O-6 substituent occupying the kinase ribose binding site. Fifty-eight O-6-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic 06 substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O-6-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site.

  DOI：

  10.1021/jm020056z

文献信息

• Synthesis of Phosphoramidite Monomers Equipped with Complementary Bases for Solid-Phase DNA Oligomerization
  作者：Sonia Romero-Pérez、Isabel López-Martín、Manuel C. Martos-Maldonado、Álvaro Somoza、David González-Rodríguez

  DOI：10.1021/acs.orglett.9b03801

  日期：2020.1.3

  bear complementary nucleobases at the edges (guanine-2'-deoxycytidine and 2-aminoadenine-2'-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their cross-coupling reactions into dinucleobase-containing monomers, and their oligomerization in the DNA synthesizer

  我们描述了两个单体的制备，该单体在边缘带有互补的碱基（鸟嘌呤2'-脱氧胞苷和2-氨基腺嘌呤-2'-脱氧尿苷），并且可以方便地保护和活化以进行固相自动DNA合成。我们报告了优化的合成途径，导致涉及的四个核碱基衍生物，它们交叉偶联反应成含二核碱基的单体，以及它们在DNA合成仪中的低聚。
• Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with <i>O</i>⁶-Substituted Guanine Derivatives
  作者：Ashleigh E. Gibson、Christine E. Arris、Johanne Bentley、F. Thomas Boyle、Nicola J. Curtin、Thomas G. Davies、Jane A. Endicott、Bernard T. Golding、Sharon Grant、Roger J. Griffin、Philip Jewsbury、Louise N. Johnson、Veronique Mesguiche、David R. Newell、Martin E. M. Noble、Julie A. Tucker、Hayley J. Whitfield

  DOI：10.1021/jm020056z

  日期：2002.8.1

  O-6-Substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B I and CDK2/cyclin A, the O-6 substituent occupying the kinase ribose binding site. Fifty-eight O-6-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic 06 substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O-6-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site.