8-acetyl-6-ethyl-7-hydroxy-4-methyl coumarin | 65490-30-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 8-acetyl-6-ethyl-7-hydroxy-4-methyl coumarin
• 英文别名: 7-hydroxy-8-acetyl-6-ethyl-4-methylcoumarin；8-acetyl-6-ethyl-7-hydroxy-4-methylcoumarin；8-acetyl-6-ethyl-7-hydroxy-4-methyl-chromen-2-one；8-acetyl-6-ethyl-7-hydroxy-4-methyl-coumarin；8-Acetyl-6-aethyl-7-hydroxy-4-methyl-cumarin；4-Methyl-6-aethyl-8-acetyl-umbelliferon；1-Methyl-6-A currencythyl-7-hydroxy-8-acetyl-cumarin；8-acetyl-6-ethyl-7-hydroxy-4-methylchromen-2-one
• CAS: 65490-30-4
• 化学式: C₁₄H₁₄O₄
• 分子量: 246.263
• InChiKey: GWHSZZFUPXTWFH-UHFFFAOYSA-N

物化性质

• 熔点：
  139 °C
• 沸点：
  453.3±45.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-acetyl-6-ethyl-7-hydroxy-4-methyl coumarin 在 氢氧化钾 、 sodium hydroxide 、 苄基三丁基氯化铵 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 46.17h， 生成
  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：

  6-乙基-7-羟基-4-甲基-2H-色烯-2-酮 在 三氯化铝 作用下， 反应 4.0h， 生成 8-acetyl-6-ethyl-7-hydroxy-4-methyl coumarin
  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

文献信息

• Thakar; Joshi, Journal of the Indian Chemical Society, 1981, vol. 58, # 9, p. 880 - 882
  作者：Thakar、Joshi

  DOI：——

  日期：——
• Thakar,K.A.; Manjaramkar,N.R., Journal of the Indian Chemical Society, 1971, vol. 48, p. 621 - 624
  作者：Thakar,K.A.、Manjaramkar,N.R.

  DOI：——

  日期：——
• Bondge; Ligde; Bhingolikar, Heterocyclic Communications, 2003, vol. 9, # 2, p. 139 - 142
  作者：Bondge、Ligde、Bhingolikar、Sonawane、Mane

  DOI：——

  日期：——
• Desai; Ekhlas, Proceedings - Indian Academy of Sciences, Section A, 1938, # 8, p. 194,199
  作者：Desai、Ekhlas

  DOI：——

  日期：——
• Marathey et al., Journal of the University of Poona, Science and Technology, 1954, # 6, p. 83,84
  作者：Marathey et al.

  DOI：——

  日期：——