4-(4-(acetamidomethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide trifluoroacetate | 1448248-70-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-(4-(acetamidomethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide trifluoroacetate
• CAS: 1448248-70-1
• 化学式: C₂HF₃O₂*C₁₅H₁₉N₅O₂S
• 分子量: 447.438
• InChiKey: TWPGQNUFDIFWHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  138.51
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride 在 吡啶 、 氨 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.17h， 生成 4-(4-(acetamidomethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide trifluoroacetate
  参考文献：
  名称：

  Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3

  摘要：

  The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e.g., 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively). Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31. Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.

  DOI：

  10.1021/jm400204k