3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D-glucopyranoside | 209746-56-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D-glucopyranoside
• 英文别名: 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D-glycopyranoside；T-1095A；3-(5-benzo[b]furanyl)-2'-(β-D-glucopyranosyloxy)-6'-hydroxy-4'-methylpropiophenone；3-(1-benzofuran-5-yl)-1-[2-hydroxy-4-methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one
• CAS: 209746-56-5
• 化学式: C₂₄H₂₆O₉
• 分子量: 458.465
• InChiKey: GMYFQAHYWIYNES-PFKOEMKTSA-N

物化性质

• 沸点：
  727.6±60.0 °C(Predicted)
• 密度：
  1.446±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  150
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D-glucopyranoside 在 2,4,6-三甲基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 Carbonic acid (2R,3S,4S,5R,6S)-6-[3-allyloxy-2-(3-benzofuran-5-yl-propionyl)-5-methyl-phenoxy]-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl ester ethyl ester
  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：

  3,5-二乙酰氧基甲苯 在 platinum on activated charcoal 4-二甲氨基吡啶 、 氢氧化钾 、 三氯化铝 、 硫酸 、 苄基三丁基氯化铵 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 55.67h， 生成 3-(benzo[b]furan-5-yl)-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

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。
• J. Med. Chem. 1999, 42, 5311-5324
  作者：

  DOI：——

  日期：——
• JPH10237089A
  申请人：——

  公开号：JPH10237089A

  公开（公告）日：1998-09-08
• US6048842A
  申请人：——

  公开号：US6048842A

  公开（公告）日：2000-04-11
• 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.