[(2'R,3S,3'R,4'S,5'R)-3',4',5'-triacetyloxy-5-[(4-methylsulfanylphenyl)methyl]spiro[1H-2-benzofuran-3,6'-oxane]-2'-yl]methyl acetate | 1395786-54-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2'R,3S,3'R,4'S,5'R)-3',4',5'-triacetyloxy-5-[(4-methylsulfanylphenyl)methyl]spiro[1H-2-benzofuran-3,6'-oxane]-2'-yl]methyl acetate
• CAS: 1395786-54-5
• 化学式: C₂₉H₃₂O₁₀S
• 分子量: 572.633
• InChiKey: MXQPXWIZUQNJDC-RQKPWJHBSA-N

物化性质

• 沸点：
  639.6±55.0 °C(predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  149
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(2'R,3S,3'R,4'S,5'R)-3',4',5'-triacetyloxy-5-[(4-methylsulfanylphenyl)methyl]spiro[1H-2-benzofuran-3,6'-oxane]-2'-yl]methyl acetate 在 甲醇 、 potassium carbonate 作用下， 反应 12.0h， 以30%的产率得到1,1-anhydro-1-C-[5-(4-methylsulfanylphenyl)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：

  (1S,3′R,4′S,5′S,6′R)-3′,4′,5′,6′-tetrahydro-6,6′-bis(hydroxymethyl)spiro[2-benzofuran-1(3H),2-[2H]pyran]-3′,4′,5′-triol 在 potassium phosphate 、 三甲基氯硅烷 、 palladium diacetate 、 三苯基膦 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 17.5h， 生成 [(2'R,3S,3'R,4'S,5'R)-3',4',5'-triacetyloxy-5-[(4-methylsulfanylphenyl)methyl]spiro[1H-2-benzofuran-3,6'-oxane]-2'-yl]methyl acetate
  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