1-(5-bromo-4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan)-5-yl)-1H-imidazol-2-yl)ethanone | 1160957-33-4

• 分子结构分类: 有机化合物
• 英文名称: 1-(5-bromo-4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan)-5-yl)-1H-imidazol-2-yl)ethanone
• 英文别名: 1-[4-bromo-5-[(4R,5S)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]-1H-imidazol-2-yl]ethanone
• CAS: 1160957-33-4
• 化学式: C₁₅H₂₁BrN₂O₅
• 分子量: 389.246
• InChiKey: YEPQPQGPHOHORG-FBIMIBRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  82.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  vinylboronic acid pinacol ester 、 1-(5-bromo-4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan)-5-yl)-1H-imidazol-2-yl)ethanone 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 cesium fluoride 、 palladium 10% on activated carbon 、 氢气 、 盐酸 、 水 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 乙醇 、 丙酮 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 19.0h， 以54%的产率得到1-(5-ethyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone
  参考文献：
  名称：

  Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders

  摘要：

  During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S I P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.

  DOI：

  10.1021/jm900278w
• 作为产物：
  描述：

  1-(5-bromo-4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan)-5-yl)-1H-imidazol-2-yl)ethanone 在 溴 、 sodium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 以93%的产率得到1-(5-bromo-4-((4S,4'R,5R)-2,2,2',2'-tetramethyl-4,4'-bi(1,3-dioxolan)-5-yl)-1H-imidazol-2-yl)ethanone
  参考文献：
  名称：

  Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders

  摘要：

  During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S I P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.

  DOI：

  10.1021/jm900278w