(4aR,5R,7S,8S,8aR)-7-(4-chloro-3-(4-methoxybenzyl)phenyl)-5-(hydroxymethyl)-2,3-dimethoxy-2,3-dimethylhexahydro-5H-pyrano[3,4-b][1,4]dioxin-8-ol | 881636-93-7

• 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: (4aR,5R,7S,8S,8aR)-7-(4-chloro-3-(4-methoxybenzyl)phenyl)-5-(hydroxymethyl)-2,3-dimethoxy-2,3-dimethylhexahydro-5H-pyrano[3,4-b][1,4]dioxin-8-ol
• CAS: 881636-93-7
• 化学式: C₂₆H₃₃ClO₈
• 分子量: 508.996
• InChiKey: REOKQSVYUHFKGT-RROIHAPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  95.84
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (4aR,5R,7S,8S,8aR)-7-(4-chloro-3-(4-methoxybenzyl)phenyl)-5-(hydroxymethyl)-2,3-dimethoxy-2,3-dimethylhexahydro-5H-pyrano[3,4-b][1,4]dioxin-8-ol 、 2-(三甲基硅烷基)乙氧甲基氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 C₃₂H₄₇ClO₉Si
  参考文献：
  名称：

  C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

  摘要：

  Modifications to the sugar portion of C-aryl glycoside sodium glucose transporter 2 (SGLT2) inhibitors were explored, including systematic deletion and modification of each of the glycoside hydroxyl groups. Based on results showing activity to be quite tolerant of structural change at the C-5 position, a series of novel C-5 spiro analogues was prepared. Some of these analogues exhibit low nanomolar potency versus SGLT2 and promote urinary glucose excretion (UGE) in rats. However, due to sub-optimal pharmacokinetic parameters (in particular half-life), predicted human doses did not meet criteria for further advancement. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.075
• 作为产物：
  描述：

  (2S,3R,4R,5S,6R)-2-(4-氯-3-(4-甲氧基苄基)苯基)-6-(羟甲基)四氢-2 、 2,3-丁二酮 、 原甲酸三甲酯 在 三氟化硼乙醚 作用下， 反应 3.0h， 生成 (4aR,5R,7S,8S,8aR)-7-(4-chloro-3-(4-methoxybenzyl)phenyl)-5-(hydroxymethyl)-2,3-dimethoxy-2,3-dimethylhexahydro-5H-pyrano[3,4-b][1,4]dioxin-8-ol
  参考文献：
  名称：

  C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

  摘要：

  Modifications to the sugar portion of C-aryl glycoside sodium glucose transporter 2 (SGLT2) inhibitors were explored, including systematic deletion and modification of each of the glycoside hydroxyl groups. Based on results showing activity to be quite tolerant of structural change at the C-5 position, a series of novel C-5 spiro analogues was prepared. Some of these analogues exhibit low nanomolar potency versus SGLT2 and promote urinary glucose excretion (UGE) in rats. However, due to sub-optimal pharmacokinetic parameters (in particular half-life), predicted human doses did not meet criteria for further advancement. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.075

文献信息

• D-pyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture
  申请人：Eckhardt Matthias

  公开号：US20060074031A1

  公开（公告）日：2006-04-06

  D-pyranosyl-substituted phenyls of general formula I wherein the groups R 1 to R 5 , X, Z and R 7a , R 7b , R 7c are defined as in claim 1, have an inhibiting effect on the sodium-dependent glucose cotransporter SGLT. The present invention also relates to pharmaceutical compositions for the treatment of metabolic disorders.

  通式I的D-吡喃基取代的苯基化合物，其中基团R1至R5、X、Z以及R7a、R7b、R7c的定义如权利要求书中所述，对依赖钠的葡萄糖共转运蛋白SGLT具有抑制作用。本发明还涉及用于治疗代谢紊乱的药物组合物。