(2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-benzofuran-5-ylmethyl)-phenyl]-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol | 1291094-09-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-benzofuran-5-ylmethyl)-phenyl]-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol
• 英文别名: USRE49080, Example 22；(2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-1-benzofuran-5-ylmethyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 1291094-09-1
• 化学式: C₂₁H₂₃ClO₆
• 分子量: 406.863
• InChiKey: YMBKJXJZFLKDDI-ADAARDCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃 在 吡啶 、 三乙基硅烷 、 4-二甲氨基吡啶 、 aluminum (III) chloride 、 正丁基锂 、 草酰氯 、 lithium hydroxide monohydrate 、 三氟化硼乙醚 、 水 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 17.75h， 生成 (2S,3R,4R,5S,6R)-2-[4-chloro-3-(2,3-dihydro-benzofuran-5-ylmethyl)-phenyl]-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol
  参考文献：
  名称：

  Design, Synthesis andin vivoEvaluation of NovelC-Aryl Glucosides as Potent Sodium-Dependent Glucose Cotransporters Inhibitors for the Treatment of Diabetes

  摘要：

  A series of novel C‐aryl glucosides with substituents at the 3′‐position or cyclization at 3′, 4′‐positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out both in normal and in streptozotocin‐induced diabetic mice. Among the synthesized compounds, compound 19a exerted potency‐similarity with dapagliflozin and triggered the hypoglycemic effect in a dose‐dependent manner. Besides, compound 19a, even at the high dose of 10 mg/kg, revealed a low risk of hypoglycemia. In further studies, 19a exhibited sustained antihyperglycemic effect without particular side‐effects in 30‐day chronic diabetic mice studies. Moreover, histological changes in the pancreas of diabetic mice indicated 19a might protect pancreatic β‐cell from apoptosis by reducing the damage of glucotoxicity. All of these results demonstrated that compound 19a, with excellent in vivo pharmacological activity and safety profile, was considered to be a promising drug candidate for the treatment of diabetes mellitus.

  DOI：

  10.1111/cbdd.12547

文献信息

• [EN] GLYCOSIDE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE GLYCOSIDE ET UTILISATIONS DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2011048112A1

  公开（公告）日：2011-04-28

  This invention relates to compounds represented by formula (I): wherein the variables are defined as herein above, which are useful for treating diseases and conditions mediated by the sodium D-glucose co-transporter (SGLT), e.g. diabetes. The invention also provides methods of treating such diseases and conditions, and compositions etc. for their treatment.

  这项发明涉及由式(I)表示的化合物，其中变量如上所定义，这些化合物对治疗由钠D-葡萄糖共转运蛋白（SGLT）介导的疾病和症状，例如糖尿病，具有益处。该发明还提供了治疗这些疾病和症状的方法，以及用于治疗的组合物等。
• Glycoside Derivatives and Uses Thereof
  申请人：BEBERNITZ Gregory Raymond

  公开号：US20110171159A1

  公开（公告）日：2011-07-14

  This invention relates to compounds represented by formula (I): wherein the variables are defined as herein above, which are useful for treating diseases and conditions mediated by the sodium D-glucose co-transporter (SGLT), e.g. diabetes. The invention also provides methods of treating such diseases and conditions, and compositions etc. for their treatment.

  这项发明涉及由式(I)表示的化合物：其中变量如上所定义，这些化合物对治疗由钠D-葡萄糖共转运蛋白（SGLT）介导的疾病和症状，例如糖尿病，具有用处。该发明还提供了治疗这些疾病和症状的方法，以及用于治疗的组合物等。
• GLYCOSIDE DERIVATIVES AND USES THEREOF
  申请人：BEBERNITZ Gregory Raymond

  公开号：US20120178680A1

  公开（公告）日：2012-07-12

  This invention relates to compounds represented by formula (I): wherein the variables are defined as herein above, which are useful for treating diseases and conditions mediated by the sodium D-glucose co-transporter (SGLT), e.g. diabetes. The invention also provides methods of treating such diseases and conditions, and compositions etc. for their treatment.

  本发明涉及由式(I)所表示的化合物：其中变量的定义如上所述，这些化合物对于治疗由钠D-葡萄糖共转运体（SGLT）介导的疾病和病状，例如糖尿病，是有用的。本发明还提供了治疗这些疾病和病状的方法、组合物等。
• US20140274921A1
  申请人：——

  公开号：US20140274921A1

  公开（公告）日：2014-09-18
• US8163704B2
  申请人：——

  公开号：US8163704B2

  公开（公告）日：2012-04-24