4'-chloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside | 257621-36-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4'-chloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside
• 英文别名: [(2R,3R,4S,5R,6S)-6-(2-acetyl-5-chloro-3-hydroxyphenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 257621-36-6
• 化学式: C₂₂H₂₅ClO₁₂
• 分子量: 516.886
• InChiKey: MEULQTFIZCOLAB-MIUGBVLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  4'-chloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢氧化钾 、 氢气 作用下， 以 乙醇 为溶剂， 生成 1-[4-Chloro-2-hydroxy-6-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-phenyl]-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-propan-1-one
  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
• 作为产物：
  描述：

  (3-Chloro-5-hydroxyphenyl) acetate 在 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 4'-chloro-2',6'-dihydroxyacetophenone 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

• Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring
  作者：Kenji Tsujihara、Mitsuya Hongu、Kunio Saito、Hiroyuki Kawanishi、Kayoko Kuriyama、Mamoru Matsumoto、Akira Oku、Kiichiro Ueta、Minoru Tsuda、Akira Saito

  DOI：10.1021/jm990175n

  日期：1999.12.1

  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.