(9aS)-8-Acetyl-1,7-dihydroxy-3-methoxy-N-(3-methoxybenzyl)-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide | 925439-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (9aS)-8-Acetyl-1,7-dihydroxy-3-methoxy-N-(3-methoxybenzyl)-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
• 英文别名: (9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-N-[(3-methoxyphenyl)methyl]-9a-methyl-9-oxodibenzofuran-4-carboxamide
• CAS: 925439-33-4
• 化学式: C₂₅H₂₃NO₈
• 分子量: 465.46
• InChiKey: QXVWPAURSSLZKZ-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide 、 3-甲氧基苯甲醛 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 8.0h， 生成 (9aS)-8-Acetyl-1,7-dihydroxy-3-methoxy-N-(3-methoxybenzyl)-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
  参考文献：
  名称：

  Discovery of a novel selective PPARγ modulator from (−)-Cercosporamide derivatives

  摘要：

  In an investigation of (-)-Cercosporamide derivatives with a plasma glucose-lowering effect, we found that N-benzylcarboxamide derivative 4 was a partial agonist of PPAR gamma. A SAR study of the substituents on carboxamide nitrogen afforded the N-(1-naphthyl) methylcarboxamide derivative 23 as the most potent selective PPAR gamma modulator. An X-ray crystallography study revealed that compound 23 bounded to the PPAR gamma ligand binding domain in a unique way without any interaction with helix12. Compound 23 displayed a potent plasma glucose-lowering effect in db/db mice without the undesirable increase in body fluid and heart weight that is typically observed when PPAR gamma full agonists are administrated. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.073

文献信息

• NOVEL CERCOSPORAMIDE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1914229B1

  公开（公告）日：2010-06-16
• Discovery of a novel selective PPARγ modulator from (−)-Cercosporamide derivatives
  作者：Akihiro Furukawa、Tsuyoshi Arita、Susumu Satoh、Kenji Wakabayashi、Shinko Hayashi、Yumi Matsui、Kazushi Araki、Masanori Kuroha、Jun Ohsumi

  DOI：10.1016/j.bmcl.2010.02.073

  日期：2010.4

  In an investigation of (-)-Cercosporamide derivatives with a plasma glucose-lowering effect, we found that N-benzylcarboxamide derivative 4 was a partial agonist of PPAR gamma. A SAR study of the substituents on carboxamide nitrogen afforded the N-(1-naphthyl) methylcarboxamide derivative 23 as the most potent selective PPAR gamma modulator. An X-ray crystallography study revealed that compound 23 bounded to the PPAR gamma ligand binding domain in a unique way without any interaction with helix12. Compound 23 displayed a potent plasma glucose-lowering effect in db/db mice without the undesirable increase in body fluid and heart weight that is typically observed when PPAR gamma full agonists are administrated. (C) 2010 Elsevier Ltd. All rights reserved.