cis-4-(3-chloro-4-methoxyphenyl)-2-cycloheptyl-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)-2-cycloheptyl-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: (4aR,8aS)-4-(3-chloro-4-methoxyphenyl)-2-cycloheptyl-4a,5,8,8a-tetrahydrophthalazin-1-one
• 化学式: C₂₂H₂₇ClN₂O₂
• 分子量: 386.922
• InChiKey: ZGBRFHWLOXQCMR-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  cis-1,2,3,6-tetrahydrophthalic anhydride 在 三氯化铝 、 sodium hydride 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 cis-4-(3-chloro-4-methoxyphenyl)-2-cycloheptyl-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。
• EP1385848A2
  申请人：——

  公开号：EP1385848A2

  公开（公告）日：2004-02-04
• US7186710B2
  申请人：——

  公开号：US7186710B2

  公开（公告）日：2007-03-06
• [EN] NOVEL PHTHALAZINONES<br/>[FR] PHTALAZINONES
  申请人：ALTANA PHARMA AG

  公开号：WO2002085906A2

  公开（公告）日：2002-10-31

  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.
• Novel Selective PDE4 Inhibitors. 2. Synthesis and Structure−Activity Relationships of 4-Aryl-Substituted <i>cis</i>-Tetra- and <i>cis</i>-Hexahydrophthalazinones
  作者：Margaretha Van der Mey、Armin Hatzelmann、Gerard P. M. Van Klink、Ivonne J. Van der Laan、Geert J. Sterk、Ulrich Thibaut、Wolf R. Ulrich、Hendrik Timmerman

  DOI：10.1021/jm010838c

  日期：2001.8.1

  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).