(cis)-4-(3,4-diethoxyphenyl)-2-{4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl}-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (cis)-4-(3,4-diethoxyphenyl)-2-{4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl}-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: (4aR,8aS)-4-(3,4-diethoxyphenyl)-2-[4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]-4a,5,8,8a-tetrahydrophthalazin-1-one
• 化学式: C₂₉H₃₂N₄O₄
• 分子量: 500.597
• InChiKey: WXBVDTBUOVXWKY-ZPUYXXQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-(4-氨基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮 在 吡啶 、 盐酸 、 sodium nitrite 作用下， 反应 8.5h， 生成 (cis)-4-(3,4-diethoxyphenyl)-2-{4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl}-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of cis-Tetrahydrophthalazinone/Pyridazinone Hybrids:  A Novel Series of Potent Dual PDE3/PDE4 Inhibitory Agents

  摘要：

  In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC(50) = 7.0-8.7), whereas the pIC(50) values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30 mumol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.

  DOI：

  10.1021/jm030776l

文献信息

• PHTHALAZINONE PDE III/IV INHIBITORS
  申请人：ALTANA Pharma AG

  公开号：EP1070056B1

  公开（公告）日：2004-06-30
• US6255303B1
  申请人：——

  公开号：US6255303B1

  公开（公告）日：2001-07-03
• Synthesis and Structure−Activity Relationships of <i>cis</i>-Tetrahydrophthalazinone/Pyridazinone Hybrids:  A Novel Series of Potent Dual PDE3/PDE4 Inhibitory Agents
  作者：Margaretha Van der Mey、Kirsten M. Bommelé、Hildegard Boss、Armin Hatzelmann、Mike Van Slingerland、Geert J. Sterk、Hendrik Timmerman

  DOI：10.1021/jm030776l

  日期：2003.5.1

  In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC(50) = 7.0-8.7), whereas the pIC(50) values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30 mumol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.