2',6'-dihydroxy-4'-methylacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside | 209746-55-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2',6'-dihydroxy-4'-methylacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside
• 英文别名: 2'-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-6'-hydroxy-4'-methylacetophenone；2'-(2,3,4,6-Tetra-acetyl-β-D-glucopyranosyloxy)-6'-hydroxy-4'-methylacetophenone；2'-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-6'-hydroxy-4'-methylacetophenone；[(2R,3R,4S,5R,6S)-6-(2-acetyl-3-hydroxy-5-methylphenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 209746-55-4
• 化学式: C₂₃H₂₈O₁₂
• 分子量: 496.468
• InChiKey: SUEPWBBNYRDKEG-DODNOZFWSA-N

物化性质

• 沸点：
  585.5±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  161
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2',6'-dihydroxy-4'-methylacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 在 platinum on activated charcoal 2,4,6-三甲基吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.67h， 生成 3-(5-benzo[b]furanyl)-2'-(6-O-methoxycarbonyl-β-D-glucopyranosyloxy)-6'-allyloxy-4'-methylpropiophenone
  参考文献：
  名称：

  Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring

  摘要：

  In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'-dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-beta-D-glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by beta-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK-A(y) mice. Additionally, long-term treatment with 5 dose-dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.

  DOI：

  10.1021/jm990175n
• 作为产物：
  描述：

  3,5-二羟基甲苯 在 吡啶 、 三氯化铝 、 苄基三丁基氯化铵 、 potassium carbonate 作用下， 以 氯仿 、 氯苯 为溶剂， 生成 2',6'-dihydroxy-4'-methylacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside
  参考文献：
  名称：

  糖基化的二氢查耳酮作为有效的和选择性的钠葡萄糖共转运蛋白2（SGLT2）抑制剂。

  摘要：

  合成了一系列葡萄糖缀合物，并测试了其对SGLT1和SGLT2的抑制作用。核心结构衍生自化合物1a。化合物1a中苯并呋喃部分和苯环的4'-取代基的修饰改善了对SGLT2的选择性。在代谢稳定性和体内功效研究中，将所选化合物与1a进行了比较。

  DOI：

  10.1016/j.bmcl.2004.07.082

文献信息

• Propiophenone derivatives and process for preparing the same
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US06048842A1

  公开（公告）日：2000-04-11

  A propiophenone derivative of the formula (I): ##STR1## wherein OX is a hydroxy group which may optionally be protected, Y is a lower alkyl group, and Z is a .beta.-D-glucopyranosyl group wherein one or more hydroxy groups may optionally be protected, or a pharmaceutically acceptable salt thereof. Said compounds have excellent hypoglycemic activity so that they are useful in the prophylaxis or treatment of diabetes.

  一种具有以下结构的丙酮苯甲酮衍生物（I）：其中OX是一个氢氧基团，可以选择性地受保护，Y是一个较低的烷基基团，Z是一个β-D-葡萄糖吡喃基团，其中一个或多个氢氧基团可以选择性地受保护，或其药用盐。这些化合物具有出色的降糖活性，因此它们在糖尿病的预防或治疗中非常有用。
• Fused heterocyclic derivative, medicinal composition containing the same, and medicinal use thereof
  申请人：Fushimi Nobuhiko

  公开号：US20060247179A1

  公开（公告）日：2006-11-02

  The present invention provides fused heterocyclic derivatives represented by the general formula: wherein R 1 represents H, halogen, OH, etc.; R 2 represents H, halogen or an alkyl group; R 3 and R 4 represent H, OH, halogen, etc.; Q represents alkylene, etc.; ring A represents aryl or heteroaryl; and G represents , or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.

  本发明提供了由通式表示的融合杂环衍生物：其中R1代表H、卤素、OH等；R2代表H、卤素或烷基；R3和R4代表H、OH、卤素等；Q代表烷基等；环A代表芳基或杂芳基；G代表，或其药学上可接受的盐，或其前药，它们在人类SGLT中表现出优异的抑制活性，并且可用作预防或治疗与高血糖有关的疾病，如糖尿病、餐后高血糖、糖耐量受损、糖尿病并发症或肥胖症的药剂，以及它们的药用组合物和药用用途。
• FUSED HETEROCYCLIC DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND MEDICINAL USE THEREOF
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1609798B1

  公开（公告）日：2012-05-09
• J. Med. Chem. 1999, 42, 5311-5324
  作者：

  DOI：——

  日期：——
• US6048842A
  申请人：——

  公开号：US6048842A

  公开（公告）日：2000-04-11