(cis)-4-(3,4-Dimethoxyphenyl)-2-(3-methoxybenzyl)-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (cis)-4-(3,4-Dimethoxyphenyl)-2-(3-methoxybenzyl)-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-one
• 英文别名: (4aR,8aS)-4-(3,4-dimethoxyphenyl)-2-[(3-methoxyphenyl)methyl]-4a,5,6,7,8,8a-hexahydrophthalazin-1-one
• 化学式: C₂₄H₂₈N₂O₄
• 分子量: 408.497
• InChiKey: RLKUDKVBRRKFID-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲氧基氯苄 、 cis-(+/-)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以85%的产率得到(cis)-4-(3,4-Dimethoxyphenyl)-2-(3-methoxybenzyl)-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Novel Selective PDE4 Inhibitors. 3. In Vivo Antiinflammatory Activity of a New Series of N-Substituted cis-Tetra- and cis-Hexahydrophthalazinones

  摘要：

  The synthesis and biological activities of a series of N-substituted cis-4a,5,6,7,8,8a-hexa- and cis-4a, 5,8,8a-tetrahydro-2H-phthalazin-1-ones are described. It was found that compounds bearing a cycloalkyl group at the 2-position exhibit the highest PDE4 inhibitory activities (pIC(50) = 8.6-9.4). The N-cycloheptyl- and N-adamantanyltetrahydrophthalazinones (7h, 8, 10, 11) show high in vivo antiinflammatory activities after oral application. Additionally, some phthalazinones were found to exhibit potent suppression of LPS-induced TNFalpha release and show moderate potency against fMLP-stimulated production of ROS.

  DOI：

  10.1021/jm0110340

文献信息

• Phthalazinones
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：US06103718A1

  公开（公告）日：2000-08-15

  Compounds of formula I wherein R1, R2, R3, R4 and R5 have the means set forth in the description are selective cyclic nucleotide phosphodiesterase (PDE) inhibitors (specifically of type 4), which are effective bronchial therapeutics.

  化学式为I的化合物，其中R1、R2、R3、R4和R5的平均值如描述中所述，是选择性环状核苷酸磷酸二酯酶（PDE）抑制剂（特别是类型4），是有效的支气管治疗药物。
• PHTHALAZINONES
  申请人：ALTANA Pharma AG

  公开号：EP0971901B1

  公开（公告）日：2003-02-26
• US6103718A
  申请人：——

  公开号：US6103718A

  公开（公告）日：2000-08-15
• Novel Selective PDE4 Inhibitors. 3. <i>In Vivo</i> Antiinflammatory Activity of a New Series of N-Substituted <i>cis</i>-Tetra- and <i>cis</i>-Hexahydrophthalazinones
  作者：Margaretha Van der Mey、Hildegard Boss、Armin Hatzelmann、Ivonne J. Van der Laan、Geert J. Sterk、Hendrik Timmerman

  DOI：10.1021/jm0110340

  日期：2002.6.1

  The synthesis and biological activities of a series of N-substituted cis-4a,5,6,7,8,8a-hexa- and cis-4a, 5,8,8a-tetrahydro-2H-phthalazin-1-ones are described. It was found that compounds bearing a cycloalkyl group at the 2-position exhibit the highest PDE4 inhibitory activities (pIC(50) = 8.6-9.4). The N-cycloheptyl- and N-adamantanyltetrahydrophthalazinones (7h, 8, 10, 11) show high in vivo antiinflammatory activities after oral application. Additionally, some phthalazinones were found to exhibit potent suppression of LPS-induced TNFalpha release and show moderate potency against fMLP-stimulated production of ROS.