2-(3-Cyclopentyloxy-4-methoxyphenyl)-5-hydroxy-2-(pyridin-4-ylmethyl)indene-1,3-dione | 203440-63-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(3-Cyclopentyloxy-4-methoxyphenyl)-5-hydroxy-2-(pyridin-4-ylmethyl)indene-1,3-dione
• CAS: 203440-63-5
• 化学式: C₂₇H₂₅NO₅
• 分子量: 443.499
• InChiKey: FQSYKPNKZQUWSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-Cyclopentyloxy-4-methoxyphenyl)-5-hydroxy-2-(pyridin-4-ylmethyl)indene-1,3-dione 在 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 [2-(3-Cyclopentyloxy-4-methoxy-phenyl)-1,3-dioxo-2-pyridin-4-ylmethyl-indan-5-yloxy]-acetic acid; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Novel Cyclic Compounds as Potent Phosphodiesterase 4 Inhibitors

  摘要：

  The synthesis and biological activity of a novel series of 2,2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.

  DOI：

  10.1021/jm970575f
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯乙酸 在 palladium on activated charcoal sodium hydroxide 、 硫酸 、 氢气 、 sodium methylate 、 乙酸酐 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 sodium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 丙酮 为溶剂， 反应 10.0h， 生成 2-(3-Cyclopentyloxy-4-methoxyphenyl)-5-hydroxy-2-(pyridin-4-ylmethyl)indene-1,3-dione
  参考文献：
  名称：

  Novel Cyclic Compounds as Potent Phosphodiesterase 4 Inhibitors

  摘要：

  The synthesis and biological activity of a novel series of 2,2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.

  DOI：

  10.1021/jm970575f

文献信息

• [EN] SUBSTITUTED AROMATIC COMPOUNDS<br/>[FR] COMPOSES AROMATIQUES SUBSTITUES
  申请人：RHONE-POULENC RORER PHARMACEUTICALS INC.

  公开号：WO1998005327A1

  公开（公告）日：1998-02-12

  (EN) This invention is directed to compound of formula (I) or hydrate thereof, solvate thereof, N-oxide thereof, prodrug thereof or a pharmaceutically acceptable salt thereof, which possess useful pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF and inhibit cyclic AMP. The present invention is also directed to their pharmaceutical use, pharmaceutical compositions containing the compounds, and methods of their preparation.(FR) La présente invention concerne un composé de la formule (I) ou un hydrate, un solvate, un N-oxyde, un promédicament ou un sel pharmaceutiquement acceptable dudit composé possédant des propriétés pharmaceutiques efficaces. Ils peuvent servir en particulier pour l'inhibition de la production ou des effets physiologiques du facteur de nécrose tumorale (TNF) et pour l'inhibition de l'AMP cyclique. La présente invention concerne également leur usage pharmaceutique, les compositions pharmaceutiques contenant de tels composés et leurs procédés de préparation.
• Novel Cyclic Compounds as Potent Phosphodiesterase 4 Inhibitors
  作者：Wei He、Fu-Chih Huang、Barbara Hanney、John Souness、Bruce Miller、Guyan Liang、Jon Mason、Stevan Djuric

  DOI：10.1021/jm970575f

  日期：1998.10.1

  The synthesis and biological activity of a novel series of 2,2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.