(1S)-1,5-anhydro-1-{5-[(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}-2-methylphenyl)methyl]-2-hydroxy-4-(propan-2-yl)phenyl}-D-glucitol | 1240304-85-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S)-1,5-anhydro-1-{5-[(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}-2-methylphenyl)methyl]-2-hydroxy-4-(propan-2-yl)phenyl}-D-glucitol
• 英文别名: (E)-N-[1-[2-(dimethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]-4-[4-[[4-hydroxy-2-propan-2-yl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]methyl]-3-methylphenyl]-2,2-dimethylbut-3-enamide
• CAS: 1240304-85-1
• 化学式: C₃₇H₅₅N₃O₈
• 分子量: 669.859
• InChiKey: AUNDWVKZNXIPOT-PZBRIFFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  172
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-异丙基苯酚 在 吡啶 、 三乙基硅烷 、 4-二甲氨基吡啶 、 potassium iodate 、 正丁基锂 、 甲烷磺酸 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 溴 、 碘 、 sodium methylate 、 palladium diacetate 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 109.42h， 生成 (1S)-1,5-anhydro-1-{5-[(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}-2-methylphenyl)methyl]-2-hydroxy-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