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

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S)-2,3,4,6-tetra-O-benzyl-1,5-anhydro-1-(3-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol
• 英文别名: methyl 2-[[3-[(2S,3S,4R,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]phenyl]methyl]azulene-1-carboxylate
• 化学式: C₅₃H₅₀O₇
• 分子量: 798.976
• InChiKey: AKQWTAPHZZTIRA-YFSBCMQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  60
• 可旋转键数：
  18
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S)-2,3,4,6-tetra-O-benzyl-1,5-anhydro-1-(3-{[1-(methoxycarbonyl)azulen-2-yl]methyl}phenyl)-D-glucitol 在 三溴化硼 、 对甲苯磺酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 5.0h， 生成 (1S)-1,5-anhydro-1-[3-(azulen-2-ylmethyl)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
• 作为产物：
  描述：

  (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[3-(hydroxymethyl)phenyl]-D-glucitol 在 三甲基氯硅烷 、 四溴化碳 、 1,2-二溴乙烷 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.5h， 生成 (1S)-2,3,4,6-tetra-O-benzyl-1,5-anhydro-1-(3-{[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

文献信息

• US7169761B2
  申请人：——

  公开号：US7169761B2

  公开（公告）日：2007-01-30
• 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
  作者：Kazuhiro Ikegai、Masakazu Imamura、Takayuki Suzuki、Keita Nakanishi、Takeshi Murakami、Eiji Kurosaki、Atsushi Noda、Yoshinori Kobayashi、Masayuki Yokota、Tomokazu Koide、Kazuhiro Kosakai、Yasufumi Ohkura、Makoto Takeuchi、Hiroshi Tomiyama、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2013.03.067

  日期：2013.7

  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.