(1S)-1,5-anhydro-1-[5-(azulen-2-ylmethyl)-2-chlorophenyl]-D-glucitol | 1443119-71-8

• 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-(azulen-2-ylmethyl)-2-chlorophenyl]-D-glucitol
• 英文别名: (2S,3R,4R,5S,6R)-2-[5-(azulen-2-ylmethyl)-2-chlorophenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 1443119-71-8
• 化学式: C₂₃H₂₃ClO₅
• 分子量: 414.886
• InChiKey: HRPXJLWLTSRHQZ-ZQGJOIPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  90.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-内酯 在 盐酸 、 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 、 三氟化硼乙醚 、 sodium methylate 、 三溴化硼 、 1,2-二溴乙烷 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 四氯化碳 、 正己烷 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 12.5h， 生成 (1S)-1,5-anhydro-1-[5-(azulen-2-ylmethyl)-2-chlorophenyl]-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

• 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.