trans-6-(3,4-dimethoxybenzoyl)cyclohex-3-enecarboxylic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: trans-6-(3,4-dimethoxybenzoyl)cyclohex-3-enecarboxylic acid
• 英文别名: (1R,6R)-6-(3,4-dimethoxybenzoyl)cyclohex-3-ene-1-carboxylic acid
• 化学式: C₁₆H₁₈O₅
• 分子量: 290.316
• InChiKey: IVDZZBBOYNNPHS-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯肼 、 trans-6-(3,4-dimethoxybenzoyl)cyclohex-3-enecarboxylic acid 以 甲苯 为溶剂， 以34%的产率得到trans-4-(3,4-dimethoxyphenyl)-2-phenyl-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
• 作为产物：
  描述：

  cis-1,2,3,6-tetrahydrophthalic anhydride 在 氢氧化钾 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 77.0h， 生成 trans-6-(3,4-dimethoxybenzoyl)cyclohex-3-enecarboxylic acid
  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

• PHTHALAZINONE PDE III/IV INHIBITORS
  申请人：ALTANA Pharma AG

  公开号：EP1070056B1

  公开（公告）日：2004-06-30
• US6255303B1
  申请人：——

  公开号：US6255303B1

  公开（公告）日：2001-07-03
• 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.