4-(4-methoxyphenyl)-3-methyl-4-oxobutanenitrile | 135312-35-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-methoxyphenyl)-3-methyl-4-oxobutanenitrile
• 英文别名: (+/-)-3-(4'-Methoxybenzoyl)-3-methylpropanonitrile；(+/-)-3-(4'-Methoxybenzoyl)-3-methylpropionitrile
• CAS: 135312-35-5
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: DJKYCQKSSQQOGI-UHFFFAOYSA-N

物化性质

• 沸点：
  386.5±22.0 °C(Predicted)
• 密度：
  1.079±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methoxyphenyl)-3-methyl-4-oxobutanenitrile 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以62%的产率得到4-(4-Hydroxy-phenyl)-3-methyl-4-oxo-butyronitrile
  参考文献：
  名称：

  (Phenylmethoxy)phenyl derivatives of w-oxo- and w-tetrazolylalkanoic acids and related tetrazoles. Synthesis and evaluation as leukotriene D4 receptor antagonists

  摘要：

  Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists. In the OMEGA-[(phenylmethoxy)phenyl]-OMEGA-oxoalkanoic acid series, 5-[4-[(4-acetyl-2-ethyl-3-hydroxyphenyl)methoxy]phenyl]-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pK(B) of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv). Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds. In the OMEGA-[5-[[(phenylmethoxy)phenyl]alkyl]tetrazolyl]alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat. The pK(B) value in the guinea pig ileum for 1-[2-hydroxy-3-propyl-4-[[4-[[2-[3-(1H-tetrazol-5-yl)propyl]-2H-tetrazol-5-yl]methyl]phenoxy]methyl]phenyl]ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv. The sodium salts of 8 (9) and 25 (26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner. Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.

  DOI：

  10.1021/jm00113a014
• 作为产物：
  描述：

  对甲氧基苯丙酮 、 溴乙腈 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 16.0h， 以60%的产率得到4-(4-methoxyphenyl)-3-methyl-4-oxobutanenitrile
  参考文献：
  名称：

  (Phenylmethoxy)phenyl derivatives of w-oxo- and w-tetrazolylalkanoic acids and related tetrazoles. Synthesis and evaluation as leukotriene D4 receptor antagonists

  摘要：

  Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists. In the OMEGA-[(phenylmethoxy)phenyl]-OMEGA-oxoalkanoic acid series, 5-[4-[(4-acetyl-2-ethyl-3-hydroxyphenyl)methoxy]phenyl]-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pK(B) of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv). Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds. In the OMEGA-[5-[[(phenylmethoxy)phenyl]alkyl]tetrazolyl]alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat. The pK(B) value in the guinea pig ileum for 1-[2-hydroxy-3-propyl-4-[[4-[[2-[3-(1H-tetrazol-5-yl)propyl]-2H-tetrazol-5-yl]methyl]phenoxy]methyl]phenyl]ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv. The sodium salts of 8 (9) and 25 (26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner. Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.

  DOI：

  10.1021/jm00113a014

文献信息

• Substituted methoxyphenyl-4,5 dihydro-3(2H)-pridazinones having
  申请人：Glaxo Inc.

  公开号：US05204463A1

  公开（公告）日：1993-04-20

  Pyridazinones of the following formula (I): ##STR1## where R.sup.1 -R.sup.4 are a variety of substituents and L is a linking group, a pharmaceutical composition for treating congestive heart failure, novel intermediates, methods for such treatment and processes for preparing compounds of formula (I).

  以下式(I)的吡啶并嗪酮：##STR1## 其中R.sup.1-R.sup.4是各种取代基，L是连接基团，用于治疗充血性心力衰竭的药物组合物，新的中间体，用于该治疗的方法以及制备式(I)化合物的过程。
• Kinetic resolution of pyridazinones using lipase
  申请人：Glaxo Inc.

  公开号：US05053338A1

  公开（公告）日：1991-10-01

  A kinetic resolution of pyridazinones of the following formula (A): ##STR1## where R.sup.1 is alkyl by enzymatic hydrolysis results in good optical purity of the phenolic product. This is significant considering the distance in the molecule (A) from the C-5 chiral center to the site of hydrolysis.

  以下化学式（A）的吡啶并氮酮：##STR1## 其中R.sup.1是烷基，通过酶水解的动力学分辨可得到良好的酚类产物光学纯度。考虑到分子（A）中C-5手性中心到水解部位的距离，这一结果具有重要意义。
• Pyridazinones having cardiotonic and beta blocking activities
  申请人：Glaxo Inc.

  公开号：US05096904A1

  公开（公告）日：1992-03-17

  Pyridazinones of the following formula (I): ##STR1## where R.sup.1 -R.sup.4 are a variety of substituents and L is a linking group, a pharmaceutical composition for treating congestive heart failure, novel intermediates, methods for such treatment and processes for preparing compounds of formula (I).

  以下是化学式（I）的吡啶并嗪酮：##STR1## 其中R.sup.1 -R.sup.4是各种取代基，L是连接基团，用于治疗充血性心力衰竭的药物组成物，新的中间体，用于这种治疗的方法和制备式（I）化合物的过程。
• Pyridazinones having cardiotonic and beta blocking activity
  申请人：GLAXO WELLCOME INC.

  公开号：EP0412814A2

  公开（公告）日：1991-02-13

  Pyridazinones of the following formula (I): where R¹-R⁴ are a variety of substituents and L is a linking group, a pharmaceutical composition for treating congestive heart failure, novel intermediates, methods for such treatment and processes for preparing compounds of formula (I).

  下式(I)的哒嗪酮： 其中 R¹-R⁴ 是各种取代基，L 是连接基团；治疗充血性心力衰竭的药物组合物、新型中间体、治疗方法和制备式 (I) 化合物的工艺。
• US5053338A
  申请人：——

  公开号：US5053338A

  公开（公告）日：1991-10-01