N-(2-methyl-1-((1-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butanamide | 1610956-94-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-methyl-1-((1-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butanamide
• 英文别名: US9688710, 147 N-(2-methyl-1-((1-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butanamide；2-methyl-N-(1-methylpiperidin-4-yl)-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide
• CAS: 1610956-94-9
• 化学式: C₃₄H₄₉N₃O₆S
• 分子量: 627.846
• InChiKey: NKIXUWMHDOVYEY-DSSMMGBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  157
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2S,3S,4R,5S,6R)-2-(3-(4-(4-methoxy-4-oxobutyl)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(2-methyl-1-((1-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butanamide
  参考文献：
  名称：

  Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes

  摘要：

  The increasing number of people afflicted with diabetes throughout the world is a major health issue. Inhibitors of the sodium dependent glucose cotransporters (SGLT) have appeared as viable therapeutics to control blood glucose levels in diabetic patents. Herein we report the discovery of LX2761, a locally acting SGLT1 inhibitor that is highly potent in vitro and delays intestinal glucose absorption in vivo to improve glycemic control.

  DOI：

  10.1021/acs.jmedchem.6b01541

文献信息

• INHIBITORS OF SODIUM GLUCOSE COTRANSPORTER 1
  申请人：LEXICON PHARMACEUTICALS, INC.

  公开号：US20160326205A1

  公开（公告）日：2016-11-10

  Inhibitors of sodium glucose cotransporter 1 (SGLT1), compositions comprising them, and methods of their use to treat diseases and disorders such as diabetes are disclosed. Particular compounds are of the formula: the various substituents of which are defined herein.

  本文披露了钠葡萄糖协同转运体1（SGLT1）的抑制剂，包括它们的组合物和使用它们治疗糖尿病等疾病和疾病的方法。具体化合物的公式为：其中各取代基在此被定义。
• Inhibitors of sodium glucose transporter 1 for constipation
  申请人：LEXICON PHARMACEUTICALS, INC.

  公开号：US10106569B2

  公开（公告）日：2018-10-23

  Inhibitors of sodium glucose cotransporter 1 (SGLT1), compositions comprising them, and methods of their use to treat diseases and disorders such as diabetes are disclosed. Particular compounds are of the formula: the various substituents of which are defined herein.

  本发明公开了钠葡萄糖共转运体 1 (SGLT1) 的抑制剂、包含这些抑制剂的组合物以及使用这些抑制剂治疗糖尿病等疾病的方法。特定化合物的化学式如下 其中的各种取代基在本文中定义。
• US9200025B2
  申请人：——

  公开号：US9200025B2

  公开（公告）日：2015-12-01
• US9688710B2
  申请人：——

  公开号：US9688710B2

  公开（公告）日：2017-06-27
• Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes
  作者：Nicole C. Goodwin、Zhi-Ming Ding、Bryce A. Harrison、Eric D. Strobel、Angela L. Harris、Melinda Smith、Andrea Y. Thompson、Wendy Xiong、Faika Mseeh、Debra J. Bruce、Damaris Diaz、Suma Gopinathan、Ling Li、Emily O’Neill、Mary Thiel、Alan G. E. Wilson、Kenneth G. Carson、David R. Powell、David B. Rawlins

  DOI：10.1021/acs.jmedchem.6b01541

  日期：2017.1.26

  The increasing number of people afflicted with diabetes throughout the world is a major health issue. Inhibitors of the sodium dependent glucose cotransporters (SGLT) have appeared as viable therapeutics to control blood glucose levels in diabetic patents. Herein we report the discovery of LX2761, a locally acting SGLT1 inhibitor that is highly potent in vitro and delays intestinal glucose absorption in vivo to improve glycemic control.