1,4-双-(3-氰基-2-甲基丙酰基)苯 | 107549-77-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1,4-双-(3-氰基-2-甲基丙酰基)苯
• 英文名称: 1,4-bis-(3-cyano-2-methylpropionyl)benzene
• 英文别名: 4-[4-(3-Cyano-2-methylpropanoyl)phenyl]-3-methyl-4-oxobutanenitrile
• CAS: 107549-77-9
• 化学式: C₁₆H₁₆N₂O₂
• 分子量: 268.315
• InChiKey: ICEAMAAUNDBLBI-UHFFFAOYSA-N

物化性质

• 熔点：
  142-146 °C
• 沸点：
  530.9±45.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-双-(3-氰基-2-甲基丙酰基)苯 在 盐酸 、 一水合肼 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 6.0h， 生成 1,4-bis(5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-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
• 作为产物：
  描述：

  1,4-Dipropionyl-benzol 在 盐酸 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 6.0h， 生成 1,4-双-(3-氰基-2-甲基丙酰基)苯
  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

• Benzene compounds having two pyridazinone substituents
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04904664A1

  公开（公告）日：1990-02-27

  The invention relates to pyridazinone derivatives which have inotropic, vasodilator and bronchodilator activity. The compounds of the invention are described by formula (I): ##STR1## wherein: R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or methyl; and represent double or single bonds; and the benzene ring is para- or meta-substituted; and pharmaceutically acceptable salts thereof.

  该发明涉及具有肌力作用、血管扩张作用和支气管扩张作用的吡啶并咪唑酮衍生物。该发明的化合物由以下式（I）描述： 其中：R.sup.1 为氢或甲基；R.sup.2 为氢或甲基；并表示双键或单键；苯环为对位或间位取代；及其药用可接受的盐。
• 6-Oxo-pyridazinyl compounds
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0208517A2

  公开（公告）日：1987-01-14

  Compounds of the formula (I) : and pharmaceutically acceptable salts are described wherein R¹ is hydrogen or methyl; R² is hydrogen or methyl; .... and ---- represent double or single bonds; and the benzene ring is para- or meta-substituted. These compounds have inotropic and vasodilator properties. Pharmaceutical compositions and methods of use are described.

  式 (I) ： 和药学上可接受的盐，其中 R¹ 是氢或甲基；R² 是氢或甲基；.... 和 ---- 代表双键或单键；苯环是对位或偏取代的。这些化合物具有肌力和血管扩张特性。描述了药物组合物和使用方法。
• 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：——
• US4904664A
  申请人：——

  公开号：US4904664A

  公开（公告）日：1990-02-27
• 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.