2-(4-(2-aminoethyl)phenoxy)-6-(2-(dimethylamino)ethoxy)-N-(3-isopropoxypropyl)pyrimidin-4-ylamine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-(2-aminoethyl)phenoxy)-6-(2-(dimethylamino)ethoxy)-N-(3-isopropoxypropyl)pyrimidin-4-ylamine
• 英文别名: 2-[4-(2-aminoethyl)phenoxy]-6-[2-(dimethylamino)ethoxy]-N-(3-propan-2-yloxypropyl)pyrimidin-4-amine
• 化学式: C₂₂H₃₅N₅O₃
• 分子量: 417.552
• InChiKey: JTSDVNJHDOBHCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  94.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N,N-二甲基乙醇胺 、 2-[4-(2-aminoethyl)phenoxy]-6-chloro-N-(3-isopropoxypropyl)pyrimidin-4-ylamine 在 N,N-二异丙基乙胺 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以56%的产率得到2-(4-(2-aminoethyl)phenoxy)-6-(2-(dimethylamino)ethoxy)-N-(3-isopropoxypropyl)pyrimidin-4-ylamine
  参考文献：
  名称：

  De Novo Design of Nonpeptidic Compounds Targeting the Interactions between Interferon-α and its Cognate Cell Surface Receptor

  摘要：

  Type 1 interferons (IFN) bind specifically to the corresponding receptor, IFNAR. Agonists and antagonists for IFNAR have potential therapeutic value in the treatment of viral infections and systemic lupus erythematosus, respectively. Specific sequences on the surface of IFN, IFN receptor recognition peptides (IRRPs) mediate the binding and signal transduction when IFN interacts with IFNAR. Structural features of two such IRRPs, IRRP-1 and IRRP-3, were used as templates to design small molecule mimetics. In silico screening was used to identify the molecular structural features mimicking their surface characteristics. A set of 26 compounds were synthesized and their ability to interfere with IFN-IFNAR interactions was investigated. Two compounds exhibited antagonist activity, specifically, blocking IFN-inducible Stat phosphorylation Stat complex-DNA binding. Design principles revealed here pave the way toward a novel series of small molecules as antagonists for IFN-IFNAR interactions.

  DOI：

  10.1021/jm701182y

文献信息

• De Novo Design of Nonpeptidic Compounds Targeting the Interactions between Interferon-α and its Cognate Cell Surface Receptor
  作者：Angelica M. Bello、Tanushree Bende、Lianhu Wei、Xiaoyang Wang、Beata Majchrzak-Kita、Eleanor N. Fish、Lakshmi P. Kotra

  DOI：10.1021/jm701182y

  日期：2008.5.1

  Type 1 interferons (IFN) bind specifically to the corresponding receptor, IFNAR. Agonists and antagonists for IFNAR have potential therapeutic value in the treatment of viral infections and systemic lupus erythematosus, respectively. Specific sequences on the surface of IFN, IFN receptor recognition peptides (IRRPs) mediate the binding and signal transduction when IFN interacts with IFNAR. Structural features of two such IRRPs, IRRP-1 and IRRP-3, were used as templates to design small molecule mimetics. In silico screening was used to identify the molecular structural features mimicking their surface characteristics. A set of 26 compounds were synthesized and their ability to interfere with IFN-IFNAR interactions was investigated. Two compounds exhibited antagonist activity, specifically, blocking IFN-inducible Stat phosphorylation Stat complex-DNA binding. Design principles revealed here pave the way toward a novel series of small molecules as antagonists for IFN-IFNAR interactions.