8-Amino-3-(benzyl-methyl-amino)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester | 185943-24-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-Amino-3-(benzyl-methyl-amino)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 8-amino-3-[benzyl(methyl)amino]-3,4-dihydro-2H-quinoline-1-carboxylate
• CAS: 185943-24-2
• 化学式: C₂₂H₂₉N₃O₂
• 分子量: 367.491
• InChiKey: CUJPWXOZPGNLMI-UHFFFAOYSA-N

物化性质

• 沸点：
  501.8±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.8
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  8-Amino-3-(benzyl-methyl-amino)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 甲酸 、 potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 25.0~110.0 ℃ 、344.73 kPa 条件下， 反应 20.0h， 生成 5,6-Dihydro-N,N-dimethyl-4H-imidazo(4,5,1-ij)quinoline-5-amine
  参考文献：
  名称：

  Synthesis and Biological Activities of (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and Its Metabolites

  摘要：

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

  DOI：

  10.1021/jm960360q
• 作为产物：
  描述：

  tert-butyl quinoline-1(2H)-carboxylate 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酰叠氮 、 水 、 氢气 、 仲丁基锂 、 sodium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， -78.0~30.0 ℃ 、344.73 kPa 条件下， 反应 7.84h， 生成 8-Amino-3-(benzyl-methyl-amino)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Activities of (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and Its Metabolites

  摘要：

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

  DOI：

  10.1021/jm960360q