1,4-bis(6-oxo-1,6-dihydropyridazin-3-yl)benzene | 107549-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,4-bis(6-oxo-1,6-dihydropyridazin-3-yl)benzene
• 英文别名: 1,4-Bis(3-oxo-2,3-dihydropyridazine-6-yl)benzene；3-[4-(6-oxo-1H-pyridazin-3-yl)phenyl]-1H-pyridazin-6-one
• CAS: 107549-65-5
• 化学式: C₁₄H₁₀N₄O₂
• 分子量: 266.259
• InChiKey: MTPSKWYBRGLEBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,4-二乙酰苯 、 乙醛酸 生成 1,4-bis(6-oxo-1,6-dihydropyridazin-3-yl)benzene
  参考文献：
  名称：

  1,4-Bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogs: potent phosphodiesterase inhibitors and inodilators

  摘要：

  1,4-Bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene and a series of related bis(azinone) compounds were synthesized. These novel compounds were evaluated for inhibition of the low Km, cAMP-selective, cGMP-inhibited phosphodiesterase (PDE III) derived from cat heart and hemodynamic activity in the ganglion- and beta-blocked anesthetized cat. The most potent PDE III inhibitor of the series was 6-[4-(5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl)-phenyl]p yridazin- 3(2H)-one (IC50 = 0.07 microM), which also retained the greatest inotrope and vasodilator (inodilator) potency (ED50 for first derivative of left ventricular pressure (dLVP/dt(max)) = 0.02 mumol/kg, ED15 for 15% fall in perfusion pressure = 0.01 mumol/kg). The structure-activity relationships observed within the bis(azinone) series were consistent with those reported for formally analogous 6-(4-substituted-phenyl)pyridazin-3(2H)-one-based PDE III-inhibiting inodilators with less-extended phenyl substituents (see e.g. Sircar et al. J. Med. Chem. 1987, 30, 1955, Moos et al. J. Med. Chem. 1987, 30, 1963). PDE III inhibitory potency is associated with overall planar topology of the phenylpyridazinone moiety and the presence of two critically separated electronegative centers. A methyl group at the 5-position of a dihydropyridazinone ring leads to enhanced potency. However, the generally higher levels of PDE III inhibitory potency shown by compounds in the bis(azinone) series relative to earlier 6-(4-substituted-phenyl)pyridazin-3(2H)-one derivatives appears to derive from a closer to optimal separation of two interacting points in the inhibitor molecule achieved through the more extended bis(azinone) structure. Correlation between the pharmacological and PDE III inhibitory activities of compounds in the bis(azinone) series provides additional evidence for PDE III being an important mediator of inodilator action.

  DOI：

  10.1021/jm00168a031

文献信息

• [EN] PHTHALAZINONE-DERIVATIVES AS PDE4 INHIBITORS<br/>[FR] DERIVES DE PHTALAZINONE UTILISES EN TANT QU'INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2005075457A1

  公开（公告）日：2005-08-18

  The compounds of a certain formula (1), in which R1, R2, R3, R9 and n have the meanings as given in the description, are novel effective PDE4 inhibitors.

  某种化学式（1）的化合物，其中R1、R2、R3、R9和n的含义如描述中所示，是新型有效的PDE4抑制剂。
• [EN] 2-(PIPERIDIN-4-YL) -4, 5-DIHYDRO-2H-PYRIDAZIN-3-ONE DERIVATIVES AS PDE4 INHIBITORS<br/>[FR] DERIVES DE 2-(PIPERIDIN-4-YL)-4,5-DIHYDRO-2H-PYRIDAZIN-3-ONE INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2005075456A1

  公开（公告）日：2005-08-18

  The compounds of a certain formula (1), in which R1, R2, R3 and R9 have the meanings as given in the description, are novel effective PDE4 inhibitors.

  具有特定公式(1)的化合物，其中R1、R2、R3和R9的含义如描述中所述，是一种新颖有效的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。
• Pyrrolidinedione substituted piperidine-phtalazones as pde4 inhibitors
  申请人：Sterk Geert Jan

  公开号：US20060160813A1

  公开（公告）日：2006-07-20

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

  具有描述中所指示的含义的取代基的I式化合物是新颖有效的PDE4抑制剂。
• Pyridazinone-derivatives as pde4 inhibitors
  申请人：Sterk Geert Jan

  公开号：US20060167001A1

  公开（公告）日：2006-07-27

  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，在给定的取代基具有描述中所给的含义时，是新颖有效的PDE4或PDE3/4抑制剂。