12-(2,5-dioxo-2H-pyrrol-1(5H)-yl)-N-(4-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxy-2-oxochroman-3-yl)methyl)phenyl)dodecanamide | 1512864-82-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 12-(2,5-dioxo-2H-pyrrol-1(5H)-yl)-N-(4-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxy-2-oxochroman-3-yl)methyl)phenyl)dodecanamide
• 英文别名: N-[4-[bis(4-hydroxy-2-oxochromen-3-yl)methyl]phenyl]-12-(2,5-dioxopyrrol-1-yl)dodecanamide
• CAS: 1512864-82-2
• 化学式: C₄₁H₄₀N₂O₉
• 分子量: 704.777
• InChiKey: YNRPLWATLYZUGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  12-(2,5-dioxo-2H-pyrrol-1(5H)-yl)dodecanoic acid 、 3-((4-aminophenyl)(4-hydroxy-2-oxochroman-3-yl)methyl)-4-hydroxy-2H-chromen-2-one 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以71%的产率得到12-(2,5-dioxo-2H-pyrrol-1(5H)-yl)-N-(4-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxy-2-oxochroman-3-yl)methyl)phenyl)dodecanamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel Dicoumarol Glucagon-like Peptide 1 Conjugates

  摘要：

  Twelve novel dicoumarol glucagon-like peptide 1 (GLP-1) conjugates were designed, synthesized, and tested for biological activity. All derivatives retained receptor activation efficacy, and exhibited improved albumin affinity and in vitro stability in rat plasma. The in vivo elimination half-lives of 13c and 131 (22.07 and 18.78 h, respectively) were much longer than those of the GLP-1 receptor agonists exendin-4 (2.82 h) and liraglutide (12.53 h). The prolonged in vivo antidiabetic effects of 13c and 13l on db/db mice were confirmed by the hypoglycemic efficacy test and the multiple intraperitoneal glucose tolerance test. Importantly, a once daily administration of 13c to db/db mice for 7 weeks provided long-term beneficial effects by lowering glycated hemoglobin (HbAlc) levels to 5.05%, which was lower than with liraglutide treatment (5.41%). These results suggest that 13c is a promising long-lasting GLP-1 mimetic that may be suitable for clinical use following further research.

  DOI：

  10.1021/jm4017448