(4aR,8aS)-5-Trimethylsilanyloxy-3,4,4a,7,8,8a-hexahydro-2H-quinoline-1-carboxylic acid tert-butyl ester | 115689-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (4aR,8aS)-5-Trimethylsilanyloxy-3,4,4a,7,8,8a-hexahydro-2H-quinoline-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4aR,8aS)-5-trimethylsilyloxy-3,4,4a,7,8,8a-hexahydro-2H-quinoline-1-carboxylate
• CAS: 115689-56-0
• 化学式: C₁₇H₃₁NO₃Si
• 分子量: 325.524
• InChiKey: LPSAUADXAHUOIC-KGLIPLIRSA-N

物化性质

• 沸点：
  367.0±42.0 °C(predicted)
• 密度：
  1.02±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4aR,8aS)-5-Trimethylsilanyloxy-3,4,4a,7,8,8a-hexahydro-2H-quinoline-1-carboxylic acid tert-butyl ester 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 甲醇 、 四氯化碳 、 氯仿 为溶剂， 反应 27.0h， 生成 (+/-)-trans-4,5,5a,6,7,8,9,9a-octahydrothiazolo<4,5-f>quinolin-2-amine
  参考文献：
  名称：

  Dopamine autoreceptor agonists as potential antipsychotics. 3. 6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine

  摘要：

  A series of rigid tricyclic analogues of the dopamine (DA) agonist PD 118440 [4-(1,2,5,6-tetrahydro-1-propyl-3-pyridinyl)-2-thiazolamine] was synthesized and evaluated for dopaminergic activity and DA autoreceptor selectivity. (R)-(+)-6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine ((+)-6) was identified as the most selective DA autoreceptor agonist from this group of compounds. It inhibited spontaneous locomotor activity (LMA) in rodents, reversed the gamma-butyrolactone (GBL) induced accumulation of rat striatal DOPA and inhibited brain DA neuronal firing, all suggestive of direct DA autoreceptor agonist activity. However, (+)-6 is not completely free of postsynaptic DA activity, as evidenced by its stimulation of LMA in rats at high doses and its ability to produce stereotypy. On the other hand, (-)-6 appears to be a weak partial DA agonist with some effects on brain DA synthesis only at high doses. Like other DA autoreceptor agonists and DA antagonists, (+)-6 inhibited Sidman conditioned avoidance in squirrel monkeys, a test predictive of clinical antipsychotic activity. However, unlike classical antipsychotics, (+)-6 did not induce dystonias in haloperidol-sensitized squirrel monkeys, suggesting a minimal propensity toward extrapyramidal side effects (EPS).

  DOI：

  10.1021/jm00113a010
• 作为产物：
  描述：

  2,3,4,6,7,8-hexahydro-5(1H)-quinolinone 在 platinum(IV) oxide sodium hydroxide 、 pyridinium dichromate 、 氢气 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， -78.0~50.0 ℃ 、3.1 MPa 条件下， 反应 164.0h， 生成 (4aR,8aS)-5-Trimethylsilanyloxy-3,4,4a,7,8,8a-hexahydro-2H-quinoline-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Dopamine autoreceptor agonists as potential antipsychotics. 3. 6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine

  摘要：

  A series of rigid tricyclic analogues of the dopamine (DA) agonist PD 118440 [4-(1,2,5,6-tetrahydro-1-propyl-3-pyridinyl)-2-thiazolamine] was synthesized and evaluated for dopaminergic activity and DA autoreceptor selectivity. (R)-(+)-6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine ((+)-6) was identified as the most selective DA autoreceptor agonist from this group of compounds. It inhibited spontaneous locomotor activity (LMA) in rodents, reversed the gamma-butyrolactone (GBL) induced accumulation of rat striatal DOPA and inhibited brain DA neuronal firing, all suggestive of direct DA autoreceptor agonist activity. However, (+)-6 is not completely free of postsynaptic DA activity, as evidenced by its stimulation of LMA in rats at high doses and its ability to produce stereotypy. On the other hand, (-)-6 appears to be a weak partial DA agonist with some effects on brain DA synthesis only at high doses. Like other DA autoreceptor agonists and DA antagonists, (+)-6 inhibited Sidman conditioned avoidance in squirrel monkeys, a test predictive of clinical antipsychotic activity. However, unlike classical antipsychotics, (+)-6 did not induce dystonias in haloperidol-sensitized squirrel monkeys, suggesting a minimal propensity toward extrapyramidal side effects (EPS).

  DOI：

  10.1021/jm00113a010