2-({4-[2-{[2-(dimethylamino)ethyl]thio}-6-(2-furyl)pyrimidin-4-yl]phenyl}thio)-N,N-dimethyl-ethanamine | 1026787-65-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-({4-[2-{[2-(dimethylamino)ethyl]thio}-6-(2-furyl)pyrimidin-4-yl]phenyl}thio)-N,N-dimethyl-ethanamine
• 英文别名: 2-[4-[2-[2-(dimethylamino)ethylsulfanyl]-6-(furan-2-yl)pyrimidin-4-yl]phenyl]sulfanyl-N,N-dimethylethanamine
• CAS: 1026787-65-4
• 化学式: C₂₂H₂₈N₄OS₂
• 分子量: 428.623
• InChiKey: GJZDNVPIQJTKHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-({4-[2-{[2-(dimethylamino)ethyl]thio}-6-(2-furyl)pyrimidin-4-yl]phenyl}thio)-N,N-dimethyl-ethanamine 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 2-({4-[2-{[2-(dimethylamino)ethyl]thio}-6-(2-furyl)pyrimidin-4-yl]phenyl}thio)-N,N-dimethylethanamine hydrochloride
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDINE COMPOUNDS AND THEIR USE AS IFNAR MEDIATORS
  [FR] COMPOSÉS DE PYRIMIDINE SUBSTITUÉS ET LEURS UTILISATIONS EN TANT QUE MÉDIATEURS D'IFNAR

  摘要：

  本申请涉及公式I的取代嘧啶化合物及其作为IFNAR配体的用途。该申请进一步涉及通过向需要的受试者施用公式(I)的这些化合物的IFNAR有效量来治疗或预防受益于通过调节IFNAR而获益的疾病或紊乱的方法。

  公开号：

  WO2009111893A1
• 作为产物：
  描述：

  N,N-dimethyl-2-<(4-bromophenyl)thio>ethylamine 、 N,N-dimethyl-2-<(4'-furan-2''-ylpyrimidin-2'-yl)thio>ethylamine 在 正丁基锂 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醚 、 四氢呋喃 为溶剂， 反应 1.92h， 以72%的产率得到2-({4-[2-{[2-(dimethylamino)ethyl]thio}-6-(2-furyl)pyrimidin-4-yl]phenyl}thio)-N,N-dimethyl-ethanamine
  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.
• [EN] SUBSTITUTED PYRIMIDINE COMPOUNDS AND THEIR USE AS IFNAR MEDIATORS<br/>[FR] COMPOSÉS DE PYRIMIDINE SUBSTITUÉS ET LEURS UTILISATIONS EN TANT QUE MÉDIATEURS D'IFNAR
  申请人：UNIV HEALTH NETWORK

  公开号：WO2009111893A1

  公开（公告）日：2009-09-17

  The present application relates to substituted pyrimidine compounds of Formula I and their use as ligands for IFNAR. The application further relates to methods of treating or preventing diseases or disorders that benefit from the modulation of IFNAR by administering an IFNAR effective amount of said compounds of Formula (I) to a subject need thereof.

  本申请涉及公式I的取代嘧啶化合物及其作为IFNAR配体的用途。该申请进一步涉及通过向需要的受试者施用公式(I)的这些化合物的IFNAR有效量来治疗或预防受益于通过调节IFNAR而获益的疾病或紊乱的方法。