N-(2-methyl-1-(4-methylpiperazin-1-yl)-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 | 1610954-95-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(2-methyl-1-(4-methylpiperazin-1-yl)-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: N-[2-methyl-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanamide
• CAS: 1610954-95-4
• 化学式: C₃₃H₄₇N₃O₆S
• 分子量: 613.819
• InChiKey: LCTZUJGQLQPULD-ZOROSQJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  甲醇 、 N-(2-methyl-1-(4-methylpiperazin-1-yl)-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 在 盐酸 作用下， 生成 methyl 2-methyl-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanoate 、 methyl 4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]phenyl]methyl]phenyl]butanoate
  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
• 作为产物：
  描述：

  (2S,3S,4R,5S,6R)-2-(3-(4-chlorobenzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 N-甲基吡咯烷酮 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-甲基二环己基胺 、 palladium 10% on activated carbon 、 氢气 、 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 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 20.0~160.0 ℃ 、2.34 MPa 条件下， 反应 1.33h， 生成 N-(2-methyl-1-(4-methylpiperazin-1-yl)-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

• [EN] INHIBITORS OF SODIUM GLUCOSE COTRANSPORTER 1<br/>[FR] INHIBITEURS DU COTRANSPORTEUR SODIUM GLUCOSE 1
  申请人：LEXICON PHARMACEUTICALS INC

  公开号：WO2014081660A1

  公开（公告）日：2014-05-30

  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 (I): the various substituents of which are defined herein.

  抑制钠葡萄糖共转运蛋白1（SGLT1）的抑制剂，包含它们的组合物，以及它们用于治疗糖尿病等疾病和紊乱的方法被披露。特定化合物的结构式如下（I）：其中各种取代基在此处被定义。
• 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 cotransporter 1
  申请人：LEXICON PHARMACEUTICALS, INC.

  公开号：US09200025B2

  公开（公告）日：2015-12-01

  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，包括它们的组合物以及使用它们治疗糖尿病等疾病和疾病的方法。特定的化合物具有以下公式：其中各取代基在此定义。
• 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