(R)-(+)-N-(4,5,5a,6,7,8-hexahydro-6-propylthiazolo<4,5-f>quinolin-2-yl)-2-amine | 115688-96-5

• 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: (R)-(+)-N-(4,5,5a,6,7,8-hexahydro-6-propylthiazolo<4,5-f>quinolin-2-yl)-2-amine
• 英文别名: (R)-6-Propyl-4,5,5a,6,7,8-hexahydro-thiazolo[4,5-f]quinolin-2-ylamine；(5aR)-6-propyl-5,5a,7,8-tetrahydro-4H-[1,3]thiazolo[4,5-f]quinolin-2-amine
• CAS: 115688-96-5
• 化学式: C₁₃H₁₉N₃S
• 分子量: 249.38
• InChiKey: VOPHHPYKMCJUCP-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  70.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (+/-)-N-(4,5,5a,6,7,8-hexahydro-6-propylthiazolo<4,5-f>quinolin-2-yl)-2-methylpropanamide 在 盐酸 作用下， 反应 2.0h， 生成 (R)-(+)-N-(4,5,5a,6,7,8-hexahydro-6-propylthiazolo<4,5-f>quinolin-2-yl)-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

文献信息

• Dopamine autoreceptor agonists as potential antipsychotics. 3. 6-Propyl-4,5,5a,6,7,8-hexahydrothiazolo[4,5-f]quinolin-2-amine
  作者：Bradley W. Caprathe、Juan C. Jaen、Lawrence D. Wise、Thomas G. Heffner、Thomas A. Pugsley、Leonard T. Meltzer、Masood Parvez

  DOI：10.1021/jm00113a010

  日期：1991.9

  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).