N⁶-cyclohexyl-2-fluoroadenine | 852231-88-0

• 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: N⁶-cyclohexyl-2-fluoroadenine
• 英文别名: 2-fluoro-6-cyclohexylaminopurine；2-fluoro-6-cyclohexylamino-purine；N-cyclohexyl-2-fluoro-7H-purin-6-amine
• CAS: 852231-88-0
• 化学式: C₁₁H₁₄FN₅
• 分子量: 235.264
• InChiKey: XKARBXJKZDKOBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N⁶-cyclohexyl-2-fluoroadenine 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 N*6*-Cyclohexyl-9-methyl-N*2*-phenyl-9H-purine-2,6-diamine
  参考文献：
  名称：

  “Reversine” and Its 2-Substituted Adenine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists

  摘要：

  The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N-6-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K-i value of 0.66 mu M. This result prompted an exploration of the structure-activity relationship of related derivatives, synthesized via sequential substitution of 6-chloro-2-fluoropurine with selected nucleophiles. Optimization of substituents at these two positions identified 2-(phenylamino)-N6-cyclohexyladenine (12), 2-(phenylamino)-N-6-cycloheptyladenine (19), and 2-phenylamino-N-6-endo-norbornyladenine (21) as potent A(3) AR ligands with K-i values of 51, 42, and 37 nM, respectively, with 30-200-fold selectivity in comparison to A(1) and A(2A) ARs. The most selective A(3) AR antagonist (> 200-fold) was 2-(phenyloxy)-N-6-cyclohexyladenine (22). 9-Methylation of 12, but not 19, was well-tolerated in A(3) AR binding. Extension of the 2-phenylamino group to 2-benzyl- and 2-(2-phenylethylamino) reduced affinity. In the series of 2-(phenylamino), 2-(phenyloxy), and 2-(phenylthio) substitutions, the order of affinity at the A(3) AR was oxy >= amino > thio. Selected derivatives, including reversine (K-B value of 466 nM via Schild analysis), competitively antagonized the functional effects of a selective A(3) AR agonist, i.e., inhibition of forskolin-stimulated cAMP production in stably transfected Chinese hamster ovary (CHO) cells. These results are in agreement with other studies suggesting the presence of a lipophilic pocket in the AR binding site that is filled by moderately sized cycloalkyl rings at the N-6 position of both adenine and adenosine derivatives. Thus, the compound series reported herein comprise an important new series of selective A(3) AR antagonists. We were unable to reproduce the dedifferentiation effect of reversine, previously reported, or to demonstrate any connection between A(3) AR antagonist effects and dedifferentiation.

  DOI：

  10.1021/jm050221l
• 作为产物：
  描述：

  环己胺 、 2-氟-6-氯嘌呤 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 12.0h， 生成 N⁶-cyclohexyl-2-fluoroadenine
  参考文献：
  名称：

  Compositions and methods for inducing cell dedifferentiation

  摘要：

  本发明提供了用于去分化定向分化的哺乳动物细胞的组成物和方法。

  公开号：

  US20050176707A1

文献信息

• Method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK)
  申请人：CHEN Han-Min

  公开号：US20140303112A1

  公开（公告）日：2014-10-09

  The present invention relates to a method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK) and the use of the compounds in the prevention or treatment of disease, including pre-diabetes, type 2 diabetes, syndrome X, metabolic syndrome and obesity.

  本发明涉及一种治疗疾病或病情的方法，该疾病或病情容易通过AMPK激活剂和公式化合物得到改善，这些化合物有助于激活AMP激活蛋白激酶（AMPK），并将这些化合物用于预防或治疗疾病，包括糖尿病前期、2型糖尿病、X综合症、代谢综合征和肥胖症。
• A “Clickable” MTX Reagent as a Practical Tool for Profiling Small-Molecule-Intracellular Target Interactions via MASPIT
  作者：Martijn D. P. Risseeuw、Dries J. H. De Clercq、Sam Lievens、Ulrik Hillaert、Davy Sinnaeve、Freya Van den Broeck、José C. Martins、Jan Tavernier、Serge Van Calenbergh

  DOI：10.1002/cmdc.201200493

  日期：2013.3

  acetylene functionalization of these baits, MFCs were synthesized via a CuAAC reaction, demonstrating the general applicability of the MTX reagent. In analytical mode, MASPIT was able to give concentration‐dependent reporter signals for the established target proteins. Furthermore, we demonstrate that the sensitivity obtained with the new MTX reagent was significantly stronger than that of a previously used

  我们提出了一种具有叠氮化物连接手柄的多功能 MTX 试剂的可扩展合成，该试剂允许快速 γ 选择性偶联产生适用于 MASPIT 的 MTX 融合化合物 (MFC)，MASPIT 是一种三杂交系统，能够识别与感兴趣的小分子。我们选择了三种结构不同的药理活性化合物（他莫昔芬、逆转素和 FK506）作为模型诱饵。在这些诱饵的乙炔官能化后，通过 CuAAC 反应合成了 MFC，证明了 MTX 试剂的普遍适用性。在分析模式下，MASPIT 能够为已建立的目标蛋白提供浓度依赖性报告信号。此外，我们证明了使用新 MTX 试剂获得的灵敏度明显强于以前使用的非区域共轭混合物。最后，在 FK506 目标的细胞阵列筛选中探索了 FK506 MFC。在近 2000 个全长人类 ORF 猎物的试点集合中，FK506 的既定目标 FKBP12 成为荧光素酶活性增加最多的猎物蛋白。这表明我们新开发的用于直接生成 MFC 的合成策略是使用
• Compositions and methods for inducing cell dedifferentiation
  申请人：Chen Shuibing

  公开号：US20050176707A1

  公开（公告）日：2005-08-11

  The present invention provides compositions and methods for dedifferentiating lineage committed mammalian cells.

  本发明提供了用于去分化定向分化的哺乳动物细胞的组成物和方法。
• Compositions and Methods for Inducing Cell Dedifferentiation
  申请人：Chen Shuibing

  公开号：US20070254884A1

  公开（公告）日：2007-11-01

  The present invention provides compositions and methods for dedifferentiating lineage committed mammalian cells.

  本发明提供了用于去分化已分化系谱哺乳动物细胞的组合物和方法。
• COMPOSITIONS AND METHODS FOR INDUCING CELL DEDIFFERENTIATION
  申请人：Chen Shuibing

  公开号：US20100022533A1

  公开（公告）日：2010-01-28

  The present invention provides compounds, compositions and methods for dedifferentiating lineage committed mammalian cells into stem cells. The present invention also provides methods of inducing dedifferentiation of lineage committed mammalian cells into stem cells, which can be further differentiated into various lineage committed cells. Methods of identifying additional compounds useful for inducing dedifferentiation of lineage committed cells into stem cells are also provided.

  本发明提供了将已分化的系谱承诺哺乳动物细胞转化为干细胞的化合物、组合物和方法。本发明还提供了诱导已分化的系谱承诺哺乳动物细胞转化为干细胞的方法，这些干细胞可以进一步分化为各种系谱承诺的细胞。本发明还提供了用于诱导已分化的系谱承诺细胞转化为干细胞的其他有用化合物的鉴定方法。