(3S,3'R,4'S,5'S,6'R)-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)-6-phenylspiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol | 1395786-44-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (3S,3'R,4'S,5'S,6'R)-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)-6-phenylspiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol
• CAS: 1395786-44-3
• 化学式: C₂₈H₃₀O₆
• 分子量: 462.543
• InChiKey: JNGSGYAKBOZRDI-DFLSAPQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 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-溴-5-氯对二甲苯 在 甲醇 、 二氯二茂钛 、 potassium fluoride 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 三甲基氯硅烷 、 1,2,3,4,5-五苯基-1′-(二叔丁基膦)二茂铁 、 偶氮二异丁腈 、 四丁基溴化铵 、 水 、 4-甲基苯磺酸吡啶 、 sodium carbonate 、 potassium carbonate 、 对甲苯磺酸 、 potassium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.83h， 生成 (3S,3'R,4'S,5'S,6'R)-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)-6-phenylspiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol
  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

• Discovery of Tofogliflozin, a Novel <i>C</i>-Arylglucoside with an <i>O</i>-Spiroketal Ring System, as a Highly Selective Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes
  作者：Yoshihito Ohtake、Tsutomu Sato、Takamitsu Kobayashi、Masahiro Nishimoto、Naoki Taka、Koji Takano、Keisuke Yamamoto、Masayuki Ohmori、Marina Yamaguchi、Kyoko Takami、Sang-Yong Yeu、Koo-Hyeon Ahn、Hiroharu Matsuoka、Kazumi Morikawa、Masayuki Suzuki、Hitoshi Hagita、Kazuharu Ozawa、Koji Yamaguchi、Motohiro Kato、Sachiya Ikeda

  DOI：10.1021/jm300884k

  日期：2012.9.13

  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.