(9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide | 925441-31-2

• 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-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
• 英文别名: (9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxodibenzofuran-4-carboxamide
• CAS: 925441-31-2
• 化学式: C₁₇H₁₅NO₇
• 分子量: 345.309
• InChiKey: MWCPUXRKEXHROH-QGZVFWFLSA-N

物化性质

• 沸点：
  526.8±50.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide 在 palladium 10% on activated carbon 4-二甲氨基吡啶 、 硫酸 、 水 、 氢气 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium nitrite 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.5h， 生成 (9aS)-8-acetyl-7-hydroxy-1,3-dimethoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
  参考文献：
  名称：

  NOVEL CERCOSPORAMIDE DERIVATIVE

  摘要：

  公开号：

  EP1914229B1
• 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 、 碘甲烷 在 potassium carbonate 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 36.0h， 以66%的产率得到(9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
  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

• Novel Cercosporamide Derivative
  申请人：Furukawa Akihiro

  公开号：US20090036492A1

  公开（公告）日：2009-02-05

  The present invention relates to a novel cercosporamide derivative, a pharmacologically acceptable salt thereof or an ester thereof which has an excellent hypoglycemic effect and is useful as a therapeutic and/or prophylactic agent for diabetes. A cercosporamide derivative having the general formula (I): [wherein X represents an oxygen atom or the like, R 1 represents a hydrogen atom or a C 1 -C 6 alkyl group, R 2 represents a hydrogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 halogenated alkyl group, R 3 represents a hydrogen atom or a C 1 -C 6 alkyl group, R 4 represents a C 6 -C 10 aryl group which may be substituted with one to five group(s) independently selected from Substituent Group a, or the like, n represents 1, 2 or 3, and Substituent Group a represents a halogen atom, a C 1 -C 6 alkyl group, a C 1 -C 6 halogenated alkyl group, a C 2 -C 6 alkenyl group, a C 2 -C 6 alkynyl group, a C 1 -C 6 alkoxy group, a C 1 -C 6 halogenated alkoxy group, a C 2 -C 6 alkenyloxy group, a C 2 -C 6 alkynyloxy group and the like], a pharmacologically acceptable salt thereof or an ester thereof.

  本发明涉及一种新型的环孢霉素衍生物，其具有优异的降血糖作用，可作为糖尿病治疗和/或预防制剂使用的药物学上可接受的盐或酯。 具有以下通式（I）的环孢霉素衍生物： [其中，X代表氧原子或类似物，R1代表氢原子或C1-C6烷基，R2代表氢原子、C1-C6烷基或C1-C6卤代烷基，R3代表氢原子或C1-C6烷基，R4代表C6-C10芳基，该芳基可被一个到五个独立选择的取代基a取代，n代表1、2或3，取代基a代表卤原子、C1-C6烷基、C1-C6卤代烷基、C2-C6烯基、C2-C6炔基、C1-C6烷氧基、C1-C6卤代烷氧基、C2-C6烯氧基、C2-C6炔氧基等]，其药学上可接受的盐或酯。
• Substituents at the naphthalene C3 position of (−)-Cercosporamide derivatives significantly affect the maximal efficacy as PPARγ partial agonists
  作者：Akihiro Furukawa、Tsuyoshi Arita、Takehiro Fukuzaki、Susumu Satoh、Makoto Mori、Takeshi Honda、Yumi Matsui、Kenji Wakabayashi、Shinko Hayashi、Kazushi Araki、Jun Ohsumi

  DOI：10.1016/j.bmcl.2011.12.066

  日期：2012.2

  Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a potential drug target for treating type 2 diabetes. The selective PPAR gamma modulators (SPPARMs), which partially activate the PPAR gamma transcriptional activity, are considered to improve the plasma glucose level with attenuated PPAR gamma related adverse effects. However, the relationships between desired pharmacological profiles and ligand specific PPAR gamma transcriptional profiles have been unclear. And there is also little knowledge of how to control ligand specific PPAR gamma transcriptional profiles. Herein, we present synthesis of novel derivatives containing substituent at naphthalene C3 position of compound 1. The novel derivatives showed various maximal efficacies as PPAR gamma partial agonist. (C) 2011 Elsevier Ltd. All rights reserved.
• 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.
• (−)-Cercosporamide derivatives as novel antihyperglycemic agents
  作者：Akihiro Furukawa、Tsuyoshi Arita、Susumu Satoh、Kazushi Araki、Masanori Kuroha、Jun Ohsumi

  DOI：10.1016/j.bmcl.2008.12.035

  日期：2009.2

  In our exploratory campaign for an antihyperglycemic agent with a novel mechanism of action, (-)-Cercosporamide 1, which is known as an antifungal agent, showed a potent plasma glucose lowering effect in hyperglycemic KK/Ta mice. The trouble was that it was accompanied by a decrease in food intake and a loss of body weight. We synthesized some (-)-Cercosporamide derivatives and succeeded to separate these actions. N,O-ketal type derivatives, especially compound 10, had the most potent plasma glucose lowering effect without affecting the food consumption or body weight. (C) 2008 Elsevier Ltd. All rights reserved.
• NOVEL CERCOSPORAMIDE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1914229B1

  公开（公告）日：2010-06-16