3-[5-(6-oxo-1H-pyridazin-3-yl)thiophen-2-yl]-1H-pyridazin-6-one | 112127-79-4

• 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: 3-[5-(6-oxo-1H-pyridazin-3-yl)thiophen-2-yl]-1H-pyridazin-6-one
• CAS: 112127-79-4
• 化学式: C₁₂H₈N₄O₂S
• 分子量: 272.287
• InChiKey: NVQFTVBILHZBCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 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：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,5-二乙酰基噻吩 生成 3-[5-(6-oxo-1H-pyridazin-3-yl)thiophen-2-yl]-1H-pyridazin-6-one
  参考文献：
  名称：

  COATES, WILLIAM J.;PRAIN, DOUGLAS H.;REEVES, MARTIN L.;WARRINGTON, BRIAN +, J. MED. CHEM., 33,(1990) N, C. 1735-1741

  摘要：

  DOI：

文献信息

• 1,4-Bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogs: potent phosphodiesterase inhibitors and inodilators
  作者：William J. Coates、H. Douglas Prain、Martin L. Reeves、Brian H. Warrington

  DOI：10.1021/jm00168a031

  日期：1990.6

  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.
• COATES, WILLIAM J.;PRAIN, DOUGLAS H.;REEVES, MARTIN L.;WARRINGTON, BRIAN +, J. MED. CHEM., 33,(1990) N, C. 1735-1741
  作者：COATES, WILLIAM J.、PRAIN, DOUGLAS H.、REEVES, MARTIN L.、WARRINGTON, BRIAN +

  DOI：——

  日期：——