1-(3-((N-phenoxycarbonyl)amino)-3-phenylpropanoyl)-4-((2-methyl-3-pyridyl)cyanomethyl)piperazine | 149692-12-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(3-((N-phenoxycarbonyl)amino)-3-phenylpropanoyl)-4-((2-methyl-3-pyridyl)cyanomethyl)piperazine
• 英文别名: 1-[3-(N-(Phenoxycarbonyl)amino)-3-phenylpropionyl]-4-[(2-methyl-pyridin-3-yl)cyanomethyl]piperazine；1-[3-(N-(Phenoxycarbonyl)amino)-3-phenylpropionyl]-4-[(2-methyl-3-pyridyl)cyanomethyl]piperazine；(3-{4-[Cyano-(2-methyl-pyridin-3-yl)-methyl]-piperazin-1-yl}-3-oxo-1-phenyl-propyl)-carbamic acid phenyl ester；phenyl N-[3-[4-[cyano-(2-methylpyridin-3-yl)methyl]piperazin-1-yl]-3-oxo-1-phenylpropyl]carbamate
• CAS: 149692-12-6
• 化学式: C₂₈H₂₉N₅O₃
• 分子量: 483.57
• InChiKey: YONUECDHHHYHOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 1-(3-((N-phenoxycarbonyl)amino)-3-phenylpropanoyl)-4-((2-methyl-3-pyridyl)cyanomethyl)piperazine 以 乙腈 为溶剂， 以66%的产率得到1-(3-(N-(1-pyrrolidinylcarbonyl)amino)-3-phenylpropanoyl)-4-((2-methyl-3-pyridyl)cyanomethyl)piperazine
  参考文献：
  名称：

  (2-Alkyl-3-pyridyl)methylpiperazine derivatives as PAF antagonists

  摘要：

  本发明涉及一般式I的新(2-烷基-3-吡啶基)甲基哌嗪衍生物，其中R¹，R²和Z如权利要求1所定义。该发明还涉及它们的制备方法以及含有它们的药物组合物。这些化合物是有效的口服PAF拮抗剂，因此它们在治疗涉及该物质的疾病中很有用。

  公开号：

  EP0528172A1
• 作为产物：
  描述：

  3-(Boc-氨基)-3-苯基丙酸 在 盐酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 1-(3-((N-phenoxycarbonyl)amino)-3-phenylpropanoyl)-4-((2-methyl-3-pyridyl)cyanomethyl)piperazine
  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