3',5'-dichloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside | 257621-52-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3',5'-dichloro-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-4,6-dichloro-3-hydroxyphenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 257621-52-6
• 化学式: C₂₂H₂₄Cl₂O₁₂
• 分子量: 551.331
• InChiKey: AOJXGZUXYUPRLF-JLMLEOCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  36
• 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：

  3',5'-dichloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 在 platinum on activated charcoal 4-二甲氨基吡啶 、 氢氧化钾 作用下， 以 乙醇 、 水 为溶剂， 反应 25.17h， 生成 3-(benzo[b]furan-5-yl)-3',5'-dichloro-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D-glucopyranoside
  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：

  2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以63%的产率得到3',5'-dichloro-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside
  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