(1S,3'R,4'S,5'R,6'R)-6'-(acetoxymethyl)-6-(chloromethyl)-3',4',5',6'-tetrahydro-3H-spiro[2-benzofuran-1,2'-pyran]-3′,4′,5′-triyl triacetate | 903566-66-5

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: (1S,3'R,4'S,5'R,6'R)-6'-(acetoxymethyl)-6-(chloromethyl)-3',4',5',6'-tetrahydro-3H-spiro[2-benzofuran-1,2'-pyran]-3′,4′,5′-triyl triacetate
• 英文别名: 1,1-anhydro-1-C-[5-chloromethyl-2-(hydroxymethyl)phenyl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose；[(2'R,3S,3'R,4'S,5'R)-3',4',5'-triacetyloxy-5-(chloromethyl)spiro[1H-2-benzofuran-3,6'-oxane]-2'-yl]methyl acetate
• CAS: 903566-66-5
• 化学式: C₂₂H₂₅ClO₁₀
• 分子量: 484.888
• InChiKey: VLDLQBYGCGVJDS-BDHVOXNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (1S,3'R,4'S,5'R,6'R)-6'-(acetoxymethyl)-6-(chloromethyl)-3',4',5',6'-tetrahydro-3H-spiro[2-benzofuran-1,2'-pyran]-3′,4′,5′-triyl triacetate 在 甲醇 、 potassium phosphate 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 27.0h， 生成 1,1-anhydro-1-C-[5-(4-hydroxyphenyl)methyl-2-(hydroxymethyl)phenyl]-β-D-glucopyranose
  参考文献：
  名称：

  Discovery of Tofogliflozin, a Novel C-Arylglucoside with an O-Spiroketal Ring System, as a Highly Selective Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition of known inhibitors. A search of the Cambridge Structural Database using a series of pharmacophore queries led to the discovery of an O-spiroketal C-arylglucoside scaffold. Subsequent chemical examination combined with computational modeling resulted in the identification of the clinical candidate 16d (CSG452, tofogliflozin), which is currently under phase III clinical trials.

  DOI：

  10.1021/jm300884k
• 作为产物：
  描述：

  [(3S,3'R,4'S,5'R,6'R)-3',4',5'-tris(phenylmethoxy)-6'-(phenylmethoxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-5-yl]methanol 在 三甲基氯硅烷 、 三氯化硼 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 4.5h， 生成 (1S,3'R,4'S,5'R,6'R)-6'-(acetoxymethyl)-6-(chloromethyl)-3',4',5',6'-tetrahydro-3H-spiro[2-benzofuran-1,2'-pyran]-3′,4′,5′-triyl triacetate
  参考文献：
  名称：

  Discovery of Tofogliflozin, a Novel C-Arylglucoside with an O-Spiroketal Ring System, as a Highly Selective Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition of known inhibitors. A search of the Cambridge Structural Database using a series of pharmacophore queries led to the discovery of an O-spiroketal C-arylglucoside scaffold. Subsequent chemical examination combined with computational modeling resulted in the identification of the clinical candidate 16d (CSG452, tofogliflozin), which is currently under phase III clinical trials.

  DOI：

  10.1021/jm300884k

文献信息

• SPIROKETAL DERIVATIVE AND USE THEREOF AS DIABETIC MEDICINE
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1852439B1

  公开（公告）日：2016-03-23