2-(1-methylethyl)-11-oxo-N-<6-(5-pyrimidinyl)hexyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-(1-methylethyl)-11-oxo-N-<6-(5-pyrimidinyl)hexyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide
• 英文别名: 11-oxo-2-propan-2-yl-N-(6-pyrimidin-5-ylhexyl)pyrido[2,1-b]quinazoline-8-carboxamide
• 化学式: C₂₆H₂₉N₅O₂
• 分子量: 443.549
• InChiKey: XMGWUMLCQPDZIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-己炔-1-醇 在 palladium on activated charcoal bis-triphenylphosphine-palladium(II) chloride 、 氯化亚砜 、 氢气 、 一水合肼 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 2-(1-methylethyl)-11-oxo-N-<6-(5-pyrimidinyl)hexyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide
  参考文献：
  名称：

  Pyrido[2,1-b]quinazolinecarboxamide derivatives as platelet activating factor antagonists

  摘要：

  A series of N-[(heteroaryl)alkyl]pyrido[2,1-b]quinazolines were evaluated for their ability to inhibit the binding of radiolabeled platelet activating factor (PAF) to its receptor on dog platelets. The most potent compounds in this series were found to be pyrido[2,1-b]quinazoline-8-carboxamides possessing a four- or six-carbon chain between the carboxamide nitrogen atom and a 3-pyridinyl or 5-pyrimidinyl moiety. Since earlier metabolism studies with pyridoquinazolinecarboxamides suggest that the carboxamide moiety is labile to hydrolysis in vivo, attempts were made to find isosteric replacements for this group. The substitutions examined led to a loss of activity; however, insertion of a methyl group on the carbon atom alpha to the carboxamide nitrogen led to an enantioselective enhancement of potency. (R)-2-(1-Methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (34) was more potent than the corresponding S enantiomer in the PAF binding assay and was also shown to be more resistant to degradation by amidases present in whole liver homogenates obtained from guinea pig, dog, and squirrel monkey. The corresponding rac-2-(1-methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (33) was found to inhibit transient PAF-induced thrombocytopenia and decreases in blood pressure in guinea pigs after intravenous or oral administration and to have a duration of action of greater than 5 h after an oral dose of 200 mg/kg. Compound 33 thus represents the prototype of a new class of orally active PAF antagonists.

  DOI：

  10.1021/jm00397a034

文献信息

• TILLEY, J. W.
  作者：TILLEY, J. W.

  DOI：——

  日期：——
• TILLEY, JEFFERSON W.;BURGHARD, BARBARA;BURGHARDT, CHARLES;MOWLES, THOMAS +, J. MED. CHEM., 31,(1988) N 2, 466-472
  作者：TILLEY, JEFFERSON W.、BURGHARD, BARBARA、BURGHARDT, CHARLES、MOWLES, THOMAS +

  DOI：——

  日期：——