4-(2-Oxo-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)piperazine-4-carbonyl)benzonitrile hydrochloride | 921616-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(2-Oxo-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)piperazine-4-carbonyl)benzonitrile hydrochloride
• 英文别名: 4-[3-oxo-4-[4-(3-piperidin-1-ylpropoxy)phenyl]piperazine-1-carbonyl]benzonitrile
• CAS: 921616-42-4
• 化学式: C₂₆H₃₀N₄O₃
• 分子量: 446.549
• InChiKey: LTJFSEMUOLPLGO-UHFFFAOYSA-N

物化性质

• 沸点：
  719.7±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  76.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-{[3-(1-piperidinyl)propyl]oxy}phenyl)-2-piperazinone trifluoroacetate 、 对氰基苯甲酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-Oxo-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)piperazine-4-carbonyl)benzonitrile hydrochloride
  参考文献：
  名称：

  4-Acyl-1-(4-aminoalkoxyphenyl)-2-ketopiperazines as a Novel Class of Non-Brain-Penetrant Histamine H₃ Receptor Antagonists

  摘要：

  A series of ketopiperazines were prepared and evaluated for their activity as histamine H-3 antagonists. From investigation of the tertiary basic center in the aminopropyloxyphenyl template, the 2(R)-methylpyrrolidine was identified as the most potent amine. In the more rigid piperidineoxyphenyl template the N-cyclobutyl group was the most potent amine. The 4-fluorobenzyol, 4-cyanobenzoyl, and 2,4-difluorobenzoyl groups provided good pharmacokinetic profiles for the various amides. The PSA and log D values of these compounds suggested low brain penetration. The compounds had very high selectivity over other receptors and did not inhibit hepatic cytochrome P450, indicating low drug-drug interaction potential. Compound 22i was identified as the best compound of this series based on its overall profile of high potency, selectivity, low brain penetration, lack of CYP450 inhibition, high oral bioavailability, and pharmacokinetic properties.

  DOI：

  10.1021/jm0708228

文献信息

• Piperazinone Derivatives Useful as Histamine H3 Receptor Antagonists and/or Inverse Agonists
  申请人：Ancliff Rachael Ann

  公开号：US20080275027A1

  公开（公告）日：2008-11-06

  The invention relates to compounds of formula (I) or salts and solvates thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis: wherein R 1 and R 2 are as defined in the specification.

  本发明涉及式(I)的化合物或其盐和溶剂化物、其制备方法、含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的应用，其中R1和R2如规范中所定义。