MB-1-12

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: MB-1-12
• 英文别名: 4-[4-[(4-Nitrophenyl)methyl]piperazin-1-yl]-2,6-dipyrrolidin-1-ylpyrimidine；4-[4-[(4-nitrophenyl)methyl]piperazin-1-yl]-2,6-dipyrrolidin-1-ylpyrimidine
• 化学式: C₂₃H₃₁N₇O₂
• 分子量: 437.545
• InChiKey: KQLWSSDYPGXCNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(1-哌嗪)-2,6-双-(1-吡咯烷)-嘧啶 、 对硝基溴化苄 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 MB-1-12
  参考文献：
  名称：

  Variation of the aryl substituent on the piperazine ring within the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases

  摘要：

  The inflammatory caspases (caspase-1, -4 and -5) are potential therapeutic targets for autoimmune and inflammatory diseases due to their involvement in the immune response upon inflammasome formation. A series of small molecules based on the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold were synthesized with varying substituents on the piperazine ring. Several compounds were pan-selective inhibitors of the inflammatory caspases, caspase-1, -4 and -5, with the ethylbenzene derivative CK-1-41 displaying low nanomolar Ki values across this family of caspases. Three analogs were nearly 10 fold selective for caspase-5 over caspase-1 and -4. The compounds display non-competitive, time dependent inhibition profiles. To our knowledge, this series is the first example of small molecule inhibitors of all three inflammatory caspases (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.025

文献信息

• Variation of the aryl substituent on the piperazine ring within the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases
  作者：Courtney R. Kent、Magdalena Bryja、Helen A. Gustafson、Margaret Y. Kawarski、Gena Lenti、Emily N. Pierce、Rachel C. Knopp、Victor Ceja、Bhabna Pati、D. Eric Walters、Caitlin E. Karver

  DOI：10.1016/j.bmcl.2016.10.025

  日期：2016.11

  The inflammatory caspases (caspase-1, -4 and -5) are potential therapeutic targets for autoimmune and inflammatory diseases due to their involvement in the immune response upon inflammasome formation. A series of small molecules based on the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold were synthesized with varying substituents on the piperazine ring. Several compounds were pan-selective inhibitors of the inflammatory caspases, caspase-1, -4 and -5, with the ethylbenzene derivative CK-1-41 displaying low nanomolar Ki values across this family of caspases. Three analogs were nearly 10 fold selective for caspase-5 over caspase-1 and -4. The compounds display non-competitive, time dependent inhibition profiles. To our knowledge, this series is the first example of small molecule inhibitors of all three inflammatory caspases (C) 2016 Elsevier Ltd. All rights reserved.