(1S)-1,5-anhydro-1-[3-(azulen-2-ylmethyl)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)-1,5-anhydro-1-[3-(azulen-2-ylmethyl)phenyl]-D-glucitol
• 英文别名: (2S,3R,4R,5S,6R)-2-[3-(azulen-2-ylmethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
• 化学式: C₂₃H₂₄O₅
• 分子量: 380.441
• InChiKey: ZZEANMDBFVJFJU-ZQGJOIPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 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

• 作为反应物：
  描述：

  (1S)-1,5-anhydro-1-[3-(azulen-2-ylmethyl)phenyl]-D-glucitol 在 aluminum (III) chloride 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 31.5h， 生成 (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-{3-[(1-acetylazulen-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
• 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 、 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-[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

文献信息

• Azulene derivatives and salts thereof
  申请人：Tomiyama Hiroshi

  公开号：US20050124555A1

  公开（公告）日：2005-06-09

  The present invention provides an azulene derivative and a salt thereof, wherein an azulene ring is bonded to a benzene ring directly or via a lower alkylene which may be substituted with a halogen atom and the benzene ring is directly bonded to the glucose residue, and it is usable as a Na + -glucose cotransporter inhibitor, especially for a therapeutic and/or preventive agent for diabetes such as insulin-dependent diabetes (type 1 diabetes) and insulin-independent diabetes (type 2 diabetes), as well as diabetes-related diseases such as insulin-resistant diseases and obesity.

  本发明提供了一种吲哚蓝衍生物及其盐，其中吲哚蓝环直接或通过可被取代为卤原子的较低烷基与苯环结合，苯环直接与葡萄糖残基结合，可用作Na+-葡萄糖共转运蛋白抑制剂，特别用于治疗和/或预防糖尿病，如胰岛素依赖型糖尿病（1型糖尿病）和胰岛素非依赖型糖尿病（2型糖尿病），以及糖尿病相关疾病，如胰岛素抵抗性疾病和肥胖症。
• AZULENE DERIVATIVES AND SALTS THEREOF
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1553094A1

  公开（公告）日：2005-07-13

  The present invention provides an azulene derivative and a salt thereof, wherein an azulene ring is bonded to a benzene ring directly or via a lower alkylene which may be substituted with a halogen atom and the benzene ring is directly bonded to the glucose residue, and it is usable as a Na+-glucose cotransporter inhibitor, especially for a therapeutic and/or preventive agent for diabetes such as insulin-dependent diabetes (type 1 diabetes) and insulin-independent diabetes (type 2 diabetes), as well as diabetes-related diseases such as insulin-resistant diseases and obesity.

  本发明提供了一种偶氮烯衍生物及其盐，其中偶氮烯环直接或通过可被卤原子取代的低级亚烷基与苯环键合，苯环直接与葡萄糖残基键合、可用作 Na+-葡萄糖共转运体抑制剂，特别是用于治疗和/或预防糖尿病，如胰岛素依赖型糖尿病（1 型糖尿病）和胰岛素非依赖型糖尿病（2 型糖尿病），以及与糖尿病相关的疾病，如胰岛素抵抗性疾病和肥胖症。
• Verwendungen von DPP IV Inhibitoren
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2407168A1

  公开（公告）日：2012-01-18

  Beschrieben wird die Verwendung ausgewählter DPP IV Inhibitoren zur Behandlung physiologischer Funktionsstörungen sowie zur Reduktion des Risikos eines Eintretens solcher Funktionsstörungen in gefährdeten Patientengruppen. Zusätzlich wird die Verwendung der genannten DPP IV Inhibitoren in Kombination mit weiteren Wirkstoffen beschrieben, wodurch verbesserte Behandlungsergebnisse erzielt werden können. Diese Verwendungen lassen sich zur Herstellung entsprechender Arzneimittel nutzen.

  本文介绍了如何使用精选的 DPP IV 抑制剂来治疗生理机能障碍，以及如何降低易感患者群体出现此类机能障碍的风险。此外，还介绍了将上述 DPP IV 抑制剂与其他活性物质结合使用，从而改善治疗效果的方法。这些用途可用于生产相应的药物。
• USES OF DPP-IV INHIBITORS
  申请人：DUGI Klaus

  公开号：US20070281940A1

  公开（公告）日：2007-12-06

  The specification describes the use of selected DPP IV inhibitors for the treatment of physiological functional disorders and for reducing the risk of the occurrence of such functional disorders in at-risk patient groups. In addition, the use of the above-mentioned DPP IV inhibitors in conjunction with other active substances is described, by means of which improved treatment outcomes can be achieved. These applications may be used to prepare corresponding medicaments.
• USES OF DPP IV INHIBITORS
  申请人：DUGI Klaus

  公开号：US20140135348A1

  公开（公告）日：2014-05-15

  The specification describes the use of selected DPP IV inhibitors for the treatment of physiological functional disorders and for reducing the risk of the occurrence of such functional disorders in at-risk patient groups. In addition, the use of the above-mentioned DPP IV inhibitors in conjunction with other active substances is described, by means of which improved treatment outcomes can be achieved. These applications may be used to prepare corresponding medicaments.