(E)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-((3aR,6S,7aS)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-2-(pyridin-4-yl)prop-2-en-1-one | 170985-18-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-((3aR,6S,7aS)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-2-(pyridin-4-yl)prop-2-en-1-one
• CAS: 170985-18-9
• 化学式: C₃₀H₃₆N₂O₅S
• 分子量: 536.692
• InChiKey: VUQWXBPQWUIQOF-ZUOHMECLSA-N

物化性质

• 沸点：
  680.2±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.32
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  85.8
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-((3aR,6S,7aS)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-2-(pyridin-4-yl)prop-2-en-1-one 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 4-[(2R)-2-(3-环戊基氧基-4-甲氧基苯基)-2-苯基乙基]吡啶
  参考文献：
  名称：

  CDP840. A prototype of a novel class of orally active anti-Inflammatory phosphodiesterase 4 inhibitors

  摘要：

  The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 29), a potent, chiral, selective inhibitor of PDE 4 (IC50 4nM). CDP840 is non-emetic in the ferret at 30 mg kg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00202-0
• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 哌啶 、 sodium hydroxide 、 氯化亚砜 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 (E)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-((3aR,6S,7aS)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-2-(pyridin-4-yl)prop-2-en-1-one
  参考文献：
  名称：

  CDP840. A prototype of a novel class of orally active anti-Inflammatory phosphodiesterase 4 inhibitors

  摘要：

  The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 29), a potent, chiral, selective inhibitor of PDE 4 (IC50 4nM). CDP840 is non-emetic in the ferret at 30 mg kg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00202-0

文献信息

• Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding
  作者：Nathalie Chauret、Daniel Guay、Chun Li、Stephen Day、José Silva、Marc Blouin、Yves Ducharme、James A. Yergey、Deborah A. Nicoll-Griffith

  DOI：10.1016/s0960-894x(02)00349-9

  日期：2002.8

  A detailed study directed towards metabolic stability optimization of the alkoxy substituents on the catechol moiety of CDP-840 is reported. Replacement of the methoxy and cyclopentyloxy substituents by cyclobutyloxy and/or difluromethoxy groups resulted in the discovery of potent and selective PDE4 inhibitors where the formation of reactive metabolites that could covalently bind to microsomal protein was significantly reduced or eliminated. (C) 2002 Elsevier Science Ltd. All rights reserved.