N-methyl-3-phenyl-succinamic acid | 73294-88-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: N-methyl-3-phenyl-succinamic acid
• 英文别名: N-Methyl-3-phenyl-succinamidsaeure；Benzenepropanoic acid, beta-((methylamino)carbonyl)-；4-(methylamino)-4-oxo-3-phenylbutanoic acid
• CAS: 73294-88-9
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: MYANGMBHBNYNQU-UHFFFAOYSA-N

物化性质

• 沸点：
  442.3±38.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methyl-3-phenyl-succinamic acid 、 1-((2-methyl-3-pyridyl)cyanomethyl)piperazine 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-{4-[Cyano-(2-methyl-pyridin-3-yl)-methyl]-piperazin-1-yl}-N-methyl-4-oxo-2-phenyl-butyramide
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists

  摘要：

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.

  DOI：

  10.1021/jm00072a019
• 作为产物：
  描述：

  甲胺 、 2-phenylsuccinic anhydride 在 乙醚 作用下， 生成 N-methyl-3-phenyl-succinamic acid 、 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  Anticonvulsants. I. An Investigation of N-R-α-R₁-α-Phenylsuccinimides

  摘要：

  DOI：

  10.1021/ja01154a126

文献信息

• Anticonvulsants. I. An Investigation of N-R-α-R₁-α-Phenylsuccinimides
  作者：C. A. Miller、Loren M. Long

  DOI：10.1021/ja01154a126

  日期：1951.10
• Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists
  作者：Elena Carceller、Manuel Merlos、Marta Giral、Carmen Almansa、Javier Bartroli、Julian Garcia-Rafanell、Javier Forn

  DOI：10.1021/jm00072a019

  日期：1993.10

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.