(cis)-4-(3-Difluoromethoxy-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-Difluoromethoxy-4-methoxyphenyl)-2-cycloheptyl-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: 3-Cycloheptyl-4aalpha,5,8,8aalpha-tetrahydro-1-[3-(difluoromethoxy)-4-methoxyphenyl]phthalazine-4(3H)-one；(4aR,8aS)-2-cycloheptyl-4-[3-(difluoromethoxy)-4-methoxyphenyl]-4a,5,8,8a-tetrahydrophthalazin-1-one
• 化学式: C₂₃H₂₈F₂N₂O₃
• 分子量: 418.484
• InChiKey: VKQDIKWPKDHRJH-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-2-(环戊基氧基)苯甲醚 在 sodium hydroxide 、 四乙基溴化铵 、 sodium hydride 、 对甲苯磺酸 、 一水合肼 、 magnesium 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 37.0h， 生成 (cis)-4-(3-Difluoromethoxy-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

• 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
• [EN] PHTHALAZINONES<br/>[FR] PHTHALAZINONES
  申请人：BYK GULDEN LOMBERG CHEMISCHE FABRIK GMBH

  公开号：WO1998031674A1

  公开（公告）日：1998-07-23

  (EN) Compounds of formula (I) wherein R1, R2, R3, R4 and R5 have the meanings as given in the description are novel effective bronchial-therapeutics.(FR) Composés représentés par la formule (I) dans laquelle R1, R2, R3, R4 et R5 possèdent les significations indiquées dans le descriptif, et constituant de nouveaux remèdes contre les affections bronchiques.
• 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).