4-(3,4-Dimethoxy-phenyl)-3-methyl-4-oxo-butyric acid | 358369-06-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3,4-Dimethoxy-phenyl)-3-methyl-4-oxo-butyric acid
• 英文别名: 4-(3,4-dimethoxyphenyl)-3-methyl-4-oxobutyric acid；4-(3,4-Dimethoxy-phenyl)-3-methyl-4-oxo-buttersaeure；[4-(3,4-dimethoxyphenyl)-3-methyl-4-oxo-butyric] acid；4-(3,4-Dimethoxyphenyl)-3-methyl-4-oxobutanoic acid
• CAS: 358369-06-9
• 化学式: C₁₃H₁₆O₅
• mdl: MFCD16432833
• 分子量: 252.267
• InChiKey: CCRYSGYQKBCXFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.384
• 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：

  4-(3,4-Dimethoxy-phenyl)-3-methyl-4-oxo-butyric acid 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以80%的产率得到3-(3,4-dimethoxyphenyl)-4-methyl-4,5-dihydro-1H-pyridazin-6-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：

  2-[2-(3,4-dimethoxyphenyl)-1-methyl-2-oxoethyl]malonic acid di(tert-butyl ester) 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 4-(3,4-Dimethoxy-phenyl)-3-methyl-4-oxo-butyric 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

• [EN] PYRIDAZINONE-DERIVATIVES AS PDE4 INHIBITORS<br/>[FR] DERIVES DE PYRIDAZINONE UTILISES COMME INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2004018451A1

  公开（公告）日：2004-03-04

  The compounds of a certain formula (1), in which the given substituents have the meanings as given in the description, are novel effective PDE4 or PDE3/4 inhibitors.

  某种化学式（1）的化合物，其中给定的取代基具有描述中给出的含义，是新颖有效的PDE4或PDE3/4抑制剂。
• [EN] PIPERIDINE-PYRIDAZONES AND PHTHALAZONES AS PDE4 INHIBITORS<br/>[FR] PIPERIDINE-PYRIDAZONES ET PHTHALAZONES EN TANT QU'INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2004017974A1

  公开（公告）日：2004-03-04

  The compounds of a certain formula 1, in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.

  某种化学式为1的化合物，其中给定的取代基具有描述中所示的含义，是新颖有效的PDE4抑制剂。
• Piperidine-pyridazones and phthalazones as pde4 inhibitors
  申请人：Sterk Geert Jan

  公开号：US20060094710A1

  公开（公告）日：2006-05-04

  The compounds of a certain formula 1, in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.

  某种化学式为1的化合物，其中给定的取代基具有描述中指定的含义，是新颖有效的PDE4抑制剂。
• 153. The constituents of natural phenolic resins. Part X. Structure of l-matairesinol dimethyl ether and observations on the condensation of reactive methylene groups with O-methyleugenol oxide
  作者：Robert D. Haworth、John R. Atkinson

  DOI：10.1039/jr9380000797

  日期：——
• Structure of Gossypol. XXIV. Attempts to Prepare Desapogossypolone Tetramethyl Ether¹
  作者：Roger Adams、T. A. Geissman、B. R. Baker、H. M. Teeter

  DOI：10.1021/ja01847a048

  日期：1941.2