1-(3-bromophenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(3-bromophenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
• 英文别名: 1-(3-bromophenyl)-2-sulfanylidene-1,3-diazinane-4,6-dione
• 化学式: C₁₀H₇BrN₂O₂S
• mdl: MFCD02194915
• 分子量: 299.148
• InChiKey: RTIYLLVUZSECDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-bromophenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione 、 5-(1-吡咯烷基)-2-糖醛 在 溶剂黄146 作用下， 反应 0.67h， 以27.1%的产率得到1-(3-bromophenyl)-5-((5-(pyrrolidin-1-yl)furan-2-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
  参考文献：
  名称：

  Small Molecule Inhibitors of Interferon‐Induced JAK‐STAT Signalling

  摘要：

  AbstractInterferons (IFN) are cytokines which, upon binding to cell surface receptors, trigger a series of downstream biochemical events including Janus Kinase (JAK) activation, phosphorylation of Signal Transducer and Activator of Transcription protein (STAT), translocation of pSTAT to the nucleus and transcriptional activation. Dysregulated IFN signalling has been linked to cancer progression and auto‐immune diseases. Here, we report the serendipitous discovery of a small molecule that blocks IFNγ activation of JAK‐STAT signalling. Further lead optimisation gave rise to a potent and more selective analogue that exerts its activity by a mechanism consistent with direct IFNγ targeting in vitro, which reduces bleeding in model of haemorrhagic colitis in vivo. This first‐in‐class small molecule also inhibits type I and III IFN‐induced STAT phosphorylation in vitro. Our work provides the basis for the development of pan‐IFN inhibitory drugs.

  DOI：

  10.1002/anie.202205231
• 作为产物：
  描述：

  1-(3-溴苯基)-2-硫脲 、 丙二酸二乙酯 在 sodium methylate 作用下， 以 甲醇 、 丙醇 为溶剂， 以52%的产率得到1-(3-bromophenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
  参考文献：
  名称：

  Small Molecule Inhibitors of Interferon‐Induced JAK‐STAT Signalling

  摘要：

  AbstractInterferons (IFN) are cytokines which, upon binding to cell surface receptors, trigger a series of downstream biochemical events including Janus Kinase (JAK) activation, phosphorylation of Signal Transducer and Activator of Transcription protein (STAT), translocation of pSTAT to the nucleus and transcriptional activation. Dysregulated IFN signalling has been linked to cancer progression and auto‐immune diseases. Here, we report the serendipitous discovery of a small molecule that blocks IFNγ activation of JAK‐STAT signalling. Further lead optimisation gave rise to a potent and more selective analogue that exerts its activity by a mechanism consistent with direct IFNγ targeting in vitro, which reduces bleeding in model of haemorrhagic colitis in vivo. This first‐in‐class small molecule also inhibits type I and III IFN‐induced STAT phosphorylation in vitro. Our work provides the basis for the development of pan‐IFN inhibitory drugs.

  DOI：

  10.1002/anie.202205231

文献信息

• WO2023/104976
  申请人：——

  公开号：——

  公开（公告）日：——