tert-Butyl 3-[4-(aminomethyl)-1H-1,2,3-triazol-1-yl]pyrrolidine-1-carboxylate | 1437385-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-Butyl 3-[4-(aminomethyl)-1H-1,2,3-triazol-1-yl]pyrrolidine-1-carboxylate
• 英文别名: tert-butyl 3-[4-(aminomethyl)triazol-1-yl]pyrrolidine-1-carboxylate
• CAS: 1437385-23-3
• 化学式: C₁₂H₂₁N₅O₂
• 分子量: 267.33
• InChiKey: IHNVTCNEHCWXIB-UHFFFAOYSA-N

物化性质

• 沸点：
  427.2±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-Butyl 3-[4-(aminomethyl)-1H-1,2,3-triazol-1-yl]pyrrolidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-((1-(1-benzylpyrrolidin-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
  参考文献：
  名称：

  Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA‐Encoded Libraries

  摘要：

  Inhibition of poly (ADP‐ribose) polymerase‐1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA‐encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA‐binding proteins, such as PARP1, can be challenging targets for DEL screening due to non‐specific protein−DNA interactions. To overcome this, we designed and screened a PARP1 catalytic domain construct without the autoinhibitory helical domain. This allowed us to interrogate an active, functionally‐relevant form of the protein resulting in the discovery of novel isoindolinone PARP1 inhibitors with single‐digit nanomolar potency. These inhibitors also demonstrated little to no PARP1−DNA trapping, a property that could be advantageous in the clinic.

  DOI：

  10.1002/cmdc.202400093