(cis)-2-Benzyl-4-(3,4-dimethoxyphenyl)-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 - 苯和取代衍生物
• 英文名称: (cis)-2-Benzyl-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: (4aR,8aS)-2-benzyl-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one
• 化学式: C₂₃H₂₄N₂O₃
• 分子量: 376.455
• InChiKey: ACCZCVFKTVIVJV-MOPGFXCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  cis-1,2,3,6-tetrahydrophthalic anhydride 在 sodium hydride 、 一水合肼 、 magnesium 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (cis)-2-Benzyl-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Novel Selective PDE4 Inhibitors. 1. Synthesis, Structure−Activity Relationships, and Molecular Modeling of 4-(3,4-Dimethoxyphenyl)-2H-phthalazin-1-ones and Analogues

  摘要：

  A number of 6-(3,4-dimethoxyphenyl)-4,5-dihydro-2H-pyridazin-3-ones and a novel series of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones were prepared and tested on the eGMP-inhibited phosphodiesterase (PDE3) and cAMP-specific phosphodiesterase (PDE4) enzymes. All tested compounds were found to specifically inhibit PDE4 except for pyridazinone 3b, which showed moderate PDE4 (pIC(50) = 6.5) as well as PDE3 (pIC(50) = 6.6) inhibitory activity. In both the pyridazinone and phthlazinone series it was found that N-substitution is beneficial for PDE4 inhibition, whereas in the pyridazinone series it also accounts for PDE4 selectivity. In the phthalazinone series, the cis-4a,5,6,7,8,8a-hexahydrophthalazinones and their corresponding 4a,5,8,8a-tetrahydro analogues showed potent PDE4 inhibitory potency (10/11c,d: pIC(50) = 7.6-8.4). A molecular modeling study revealed that the cis-fused cyclohexa(e)ne rings occupy a region in space different from that occupied by the other fused (un)saturated hydrocarbon rings applied; we therefore assume that the steric interactions of these rings with the binding site play an important role in enzyme inhibition.

  DOI：

  10.1021/jm010837k

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
• [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. 1. Synthesis, Structure−Activity Relationships, and Molecular Modeling of 4-(3,4-Dimethoxyphenyl)-2<i>H</i>-phthalazin-1-ones and Analogues
  作者：Margaretha Van der Mey、Armin Hatzelmann、Ivonne J. Van der Laan、Geert J. Sterk、Ulrich Thibaut、Hendrik Timmerman

  DOI：10.1021/jm010837k

  日期：2001.8.1

  A number of 6-(3,4-dimethoxyphenyl)-4,5-dihydro-2H-pyridazin-3-ones and a novel series of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones were prepared and tested on the eGMP-inhibited phosphodiesterase (PDE3) and cAMP-specific phosphodiesterase (PDE4) enzymes. All tested compounds were found to specifically inhibit PDE4 except for pyridazinone 3b, which showed moderate PDE4 (pIC(50) = 6.5) as well as PDE3 (pIC(50) = 6.6) inhibitory activity. In both the pyridazinone and phthlazinone series it was found that N-substitution is beneficial for PDE4 inhibition, whereas in the pyridazinone series it also accounts for PDE4 selectivity. In the phthalazinone series, the cis-4a,5,6,7,8,8a-hexahydrophthalazinones and their corresponding 4a,5,8,8a-tetrahydro analogues showed potent PDE4 inhibitory potency (10/11c,d: pIC(50) = 7.6-8.4). A molecular modeling study revealed that the cis-fused cyclohexa(e)ne rings occupy a region in space different from that occupied by the other fused (un)saturated hydrocarbon rings applied; we therefore assume that the steric interactions of these rings with the binding site play an important role in enzyme inhibition.