potassium (9bs)-2-acetyl-6-([(2-ethyl-4-fluoronaphthalen-1-yl)methyl]carbamoyl)-9-hydroxy-7-methoxy-9b-methyl-1-oxo-1,9b-dihydrodibenzo[b,d]furan-3-olate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: potassium (9bs)-2-acetyl-6-([(2-ethyl-4-fluoronaphthalen-1-yl)methyl]carbamoyl)-9-hydroxy-7-methoxy-9b-methyl-1-oxo-1,9b-dihydrodibenzo[b,d]furan-3-olate
• 英文别名: potassium;(9bS)-2-acetyl-6-[(2-ethyl-4-fluoronaphthalen-1-yl)methylcarbamoyl]-9-hydroxy-7-methoxy-9b-methyl-1-oxodibenzofuran-3-olate
• 化学式: C₃₀H₂₅FNO₇*K
• 分子量: 569.628
• InChiKey: XIHZEVNIIWVEAO-VNUFCWELSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.51
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (9aS)-8-乙酰基-1,3,7-三羟基-9a-甲基-9-氧代二苯并呋喃-4-甲酰胺 在 三乙基硅烷 、 potassium carbonate 、 三氟乙酸 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.5h， 生成 potassium (9bs)-2-acetyl-6-([(2-ethyl-4-fluoronaphthalen-1-yl)methyl]carbamoyl)-9-hydroxy-7-methoxy-9b-methyl-1-oxo-1,9b-dihydrodibenzo[b,d]furan-3-olate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel (−)-cercosporamide derivatives as potent selective PPARγ modulators

  摘要：

  Selective peroxisome proliferator-activated receptor gamma (PPAR gamma) modulators are expected to be a novel class of drugs improving plasma glucose levels without PPAR gamma-related adverse effects. As a continuation of our studies for (-)-Cercosporamide derivatives as selective PPAR gamma modulators, we synthesized substituted naphthalene type compounds and identified the most potent compound 15 (EC50 = 0.94 nM, E-max), = 38%). Compound 15 selectively activated PPAR gamma transcription and did not activate PPAR alpha and PPAR delta. The potassium salt of compound 15 showed a high solubility and a good oral bioavailability (58%). Oral administration of the potassium salt remarkably improved the plasma glucose levels of female Zucker diabetic fatty rats at 1 mg/kg. Moreover, it did not cause a plasma volume increase or a cardiac enlargement in Wistar-Imamichi rats, even at 100 mg/kg. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.040

文献信息

• Synthesis and biological evaluation of novel (−)-cercosporamide derivatives as potent selective PPARγ modulators
  作者：Akihiro Furukawa、Tsuyoshi Arita、Takehiro Fukuzaki、Makoto Mori、Takeshi Honda、Susumu Satoh、Yumi Matsui、Kenji Wakabayashi、Shinko Hayashi、Kouichi Nakamura、Kazushi Araki、Masanori Kuroha、Jun Tanaka、Satoko Wakimoto、Osamu Suzuki、Jun Ohsumi

  DOI：10.1016/j.ejmech.2012.05.040

  日期：2012.8

  Selective peroxisome proliferator-activated receptor gamma (PPAR gamma) modulators are expected to be a novel class of drugs improving plasma glucose levels without PPAR gamma-related adverse effects. As a continuation of our studies for (-)-Cercosporamide derivatives as selective PPAR gamma modulators, we synthesized substituted naphthalene type compounds and identified the most potent compound 15 (EC50 = 0.94 nM, E-max), = 38%). Compound 15 selectively activated PPAR gamma transcription and did not activate PPAR alpha and PPAR delta. The potassium salt of compound 15 showed a high solubility and a good oral bioavailability (58%). Oral administration of the potassium salt remarkably improved the plasma glucose levels of female Zucker diabetic fatty rats at 1 mg/kg. Moreover, it did not cause a plasma volume increase or a cardiac enlargement in Wistar-Imamichi rats, even at 100 mg/kg. (C) 2012 Elsevier Masson SAS. All rights reserved.