(1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-fluoro-5-(hydroxymethyl)phenyl]-D-glucitol | 655237-59-5

• 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-2,3,4,6-tetra-O-benzyl-1-[2-fluoro-5-(hydroxymethyl)phenyl]-D-glucitol
• 英文别名: [4-fluoro-3-[(2S,3S,4R,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]phenyl]methanol
• CAS: 655237-59-5
• 化学式: C₄₁H₄₁FO₆
• 分子量: 648.771
• InChiKey: DBFFNAWPFMIOFN-XGLMOPDYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-fluoro-5-(hydroxymethyl)phenyl]-D-glucitol 在 三甲基氯硅烷 、 四溴化碳 、 三溴化硼 、 对甲苯磺酸 、 1,2-二溴乙烷 、 三苯基膦 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 20.5h， 生成 (1S)-1,5-anhydro-1-[5-(azulen-2-ylmethyl)-2-fluorophenyl]-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：

  5-内酯 在 正丁基锂 、 三异丙基硅烷 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 3.5h， 生成 (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-fluoro-5-(hydroxymethyl)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

文献信息

• US7169761B2
  申请人：——

  公开号：US7169761B2

  公开（公告）日：2007-01-30