(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(5-(4-((E)-3,3-dimethyl-4-((2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl)amino)-4-oxobut-1-en-1-yl)benzyl)-4-isopropyl-2-methoxyphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 1240305-18-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(5-(4-((E)-3,3-dimethyl-4-((2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl)amino)-4-oxobut-1-en-1-yl)benzyl)-4-isopropyl-2-methoxyphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• 英文别名: (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[5-({4-[(1E)-3,3-dimethyl-4-{[2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl]amino}-4-oxobut-1-en-1-yl]phenyl}methyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol
• CAS: 1240305-18-3
• 化学式: C₄₅H₆₁N₃O₁₂
• 分子量: 835.992
• InChiKey: MCTXTIGFUOURFR-FHSMDKKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  60.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  185.1
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(5-(4-((E)-3,3-dimethyl-4-((2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl)amino)-4-oxobut-1-en-1-yl)benzyl)-4-isopropyl-2-methoxyphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以70%的产率得到(1S)-1,5-anhydro-1-[5-({4-[(1E)-3,3-dimethyl-4-{[2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl]amino}-4-oxobut-1-en-1-yl]phenyl}methyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol
  参考文献：
  名称：

  Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment

  摘要：

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.

  DOI：

  10.1016/j.bmc.2018.12.015
• 作为产物：
  描述：

  2,2-二甲基-3-丁烯酸 在 草酰氯 、 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二甲基甲酰胺 、 三(邻甲基苯基)磷 、 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(5-(4-((E)-3,3-dimethyl-4-((2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl)amino)-4-oxobut-1-en-1-yl)benzyl)-4-isopropyl-2-methoxyphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment

  摘要：

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.

  DOI：

  10.1016/j.bmc.2018.12.015