(9aS)-8-acetyl-N-[(4-chloro-2-methylnaphthalen-1-yl)methyl]-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide | 925441-12-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (9aS)-8-acetyl-N-[(4-chloro-2-methylnaphthalen-1-yl)methyl]-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide
• 英文别名: (9aS)-8-acetyl-N-[(4-chloro-2-methyl-1-naphthyl)methyl]-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide；(9aS)-8-acetyl-N-[(4-chloro-2-methylnaphthalen-1-yl)methyl]-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxodibenzofuran-4-carboxamide
• CAS: 925441-12-9
• 化学式: C₂₉H₂₄ClNO₇
• 分子量: 533.965
• InChiKey: TURKOZADAUULDM-GDLZYMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

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 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.0h， 生成 (9aS)-8-acetyl-N-[(4-chloro-2-methylnaphthalen-1-yl)methyl]-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。
• NOVEL CERCOSPORAMIDE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1914229B1

  公开（公告）日：2010-06-16
• 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.