(cis)-4-(3-Chloro-4-methoxyphenyl)-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-Chloro-4-methoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: (4aR,8aS)-4-(3-chloro-4-methoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 化学式: C₁₅H₁₅ClN₂O₂
• 分子量: 290.749
• InChiKey: MGODEOQJXGJNKA-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (cis)-4-(3-Chloro-4-methoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one 在 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 cis-4-(3-chloro-4-methoxyphenyl)-2-{4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenoxy]butyl}-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
• 作为产物：
  描述：

  cis-1,2,3,6-tetrahydrophthalic anhydride 在 三氯化铝 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (cis)-4-(3-Chloro-4-methoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Novel Selective PDE4 Inhibitors. 2. Synthesis and Structure−Activity Relationships of 4-Aryl-Substituted cis-Tetra- and cis-Hexahydrophthalazinones

  摘要：

  A series of 4-aryl-substituted cis-4a,5,8,8a-tetra- and cis-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-ones with high inhibitory activity toward cAMP-specific phosphodiesterase (PDE4) was synthesized. To study structure-activity relationships various substituents were introduced to the 2-, 3-, and 4-positions of the 4-phenyl ring. Substitution at the 4-position of the phenyl ring was restricted to a methoxy group, probably due to unfavorable steric interactions of larger groups with the binding site. The introduction of many alkoxy substituents including distinct ring systems and functional groups was allowed to the 3-position. It was found that in general the cis-4a,5,8,8a-tetrahydro-2H-phthalazin-1-ones are more potent than their hexahydrophthalic counterparts, the best activity residing in (4-imidazol-1-yl-phenoxy)butoxy analogue 16o (pIC(50) = 9.7).

  DOI：

  10.1021/jm010838c

文献信息

• Novel phthalazinones
  申请人：——

  公开号：US20040127707A1

  公开（公告）日：2004-07-01

  The compounds of formula I in which R1, R2, R3, R4 and R5 have the meanings as given in the description are PDE4/7 inhibitors.

  式I中，当R1、R2、R3、R4和R5的含义如描述所述时，这些化合物是PDE4/7抑制剂。
• PHTHALAZINONE PDE III/IV INHIBITORS
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：EP1070056A1

  公开（公告）日：2001-01-24
• EP1385848A2
  申请人：——

  公开号：EP1385848A2

  公开（公告）日：2004-02-04
• US6255303B1
  申请人：——

  公开号：US6255303B1

  公开（公告）日：2001-07-03
• US7186710B2
  申请人：——

  公开号：US7186710B2

  公开（公告）日：2007-03-06