(1S)-1,5-anhydro-2,3,4,6-tetra-O-acetyl-1-(2-acetoxy-5-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol | 1443119-75-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S)-1,5-anhydro-2,3,4,6-tetra-O-acetyl-1-(2-acetoxy-5-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol
• CAS: 1443119-75-2
• 化学式: C₃₅H₃₆O₁₃
• 分子量: 664.663
• InChiKey: SSWGIMFBKDZTLQ-SDHGQUHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.89
• 重原子数：
  48.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  167.03
• 氢给体数：
  0.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (1S)-1,5-anhydro-2,3,4,6-tetra-O-acetyl-1-(2-acetoxy-5-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 5.67h， 以53%的产率得到(1S)-1,5-anhydro-1-[5-(azulen-2-ylmethyl)-2-hydroxyphenyl]-D-glucitol
  参考文献：
  名称：

  Synthesis and biological evaluation of C-glucosides with azulene rings as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus: Discovery of YM543

  摘要：

  Here, a series of C-glucosides with azulene rings in the aglycon moiety was synthesized and the inhibitory activities toward hSGLT1 and hSGLT2 were evaluated. Starting from the azulene derivative 7 which had relatively good SGLT2 inhibitory activity, compound 8a which has a 3-[(azulen-2-yl)methyl]phenyl group was identified as a lead compound for further optimization. Introduction of a phenolic hydroxyl group onto the central benzene ring afforded a potent and selective SGLT2 inhibitor 8e, which reduced blood glucose levels in a dose-dependent manner in rodent diabetic models. A mono choline salt of 8e (YM543) was selected as a clinical candidate for use in treating type 2 diabetes mellitus. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.067
• 作为产物：
  描述：

  1-(苄氧基)-2-溴-4-甲基苯 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 三甲基氯硅烷 、 偶氮二异丁腈 、 三异丙基硅烷 、 20 %mol Pd(OH)2/C 、 三氟化硼乙醚 、 氢气 、 1,2-二溴乙烷 、 锌 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， -78.0~80.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成 (1S)-1,5-anhydro-2,3,4,6-tetra-O-acetyl-1-(2-acetoxy-5-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol
  参考文献：
  名称：

  Synthesis and biological evaluation of C-glucosides with azulene rings as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus: Discovery of YM543

  摘要：

  Here, a series of C-glucosides with azulene rings in the aglycon moiety was synthesized and the inhibitory activities toward hSGLT1 and hSGLT2 were evaluated. Starting from the azulene derivative 7 which had relatively good SGLT2 inhibitory activity, compound 8a which has a 3-[(azulen-2-yl)methyl]phenyl group was identified as a lead compound for further optimization. Introduction of a phenolic hydroxyl group onto the central benzene ring afforded a potent and selective SGLT2 inhibitor 8e, which reduced blood glucose levels in a dose-dependent manner in rodent diabetic models. A mono choline salt of 8e (YM543) was selected as a clinical candidate for use in treating type 2 diabetes mellitus. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.067