2-methyl (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate | 157521-46-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-methyl (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate
• 英文别名: 1-O-benzyl 2-O-methyl (2S)-3,4-dihydro-2H-quinoline-1,2-dicarboxylate
• CAS: 157521-46-5
• 化学式: C₁₉H₁₉NO₄
• 分子量: 325.364
• InChiKey: YVJGKBPFESLCDT-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate 在 四溴化碳 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 29.0h， 生成 (S)-(-)-N-(4-(4-m-tolylpiperazin-1-yl)butyl)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxamide
  参考文献：
  名称：

  Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies

  摘要：

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.

  DOI：

  10.1021/jm501119j
• 作为产物：
  描述：

  1,2,3,4-四氢喹啉-2-羧酸 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-methyl (S)-(-)-1-(benzyloxycarbonyl)-1,2,3,4-tetrahydroquinoline-2-carboxylate
  参考文献：
  名称：

  构象受限的二肽模拟物的苯并稠合，7,5-和7,6-稠合的pin庚酮的合成

  摘要：

  已经开发了用于产生新的构象受限的二肽模拟物9和16的方法。关键步骤涉及在近端二氢吲哚/四氢喹啉芳族环中分子内添加氧鎓离子。在7，5-与7，6-融合的氮杂pin酮核的形成中观察到反应性的显着差异。描述了这些模拟物在合成双作用ACE / NEP抑制剂1和2中的应用。

  DOI：

  10.1016/0040-4039(95)00096-u

文献信息

• Novel Aryl Piperazine Derivatives With Medical Utility
  申请人：Campiani Giuseppe

  公开号：US20090238761A1

  公开（公告）日：2009-09-24

  This invention provides novel aryl piperazine derivatives having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D 3 , D 2 -like and 5-HT 2 receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders incl. schizophrenia.

  这项发明提供了具有医疗效用的新型芳基哌嗪衍生物，特别是作为多巴胺和5-羟色胺受体的调节剂，优选为D3、D2样和5-HT2受体亚型，特别适用于治疗包括精神分裂症在内的神经精神障碍。
• Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies
  作者：Margherita Brindisi、Stefania Butini、Silvia Franceschini、Simone Brogi、Francesco Trotta、Sindu Ros、Alfredo Cagnotto、Mario Salmona、Alice Casagni、Marco Andreassi、Simona Saponara、Beatrice Gorelli、Pia Weikop、Jens D. Mikkelsen、Jorgen Scheel-Kruger、Karin Sandager-Nielsen、Ettore Novellino、Giuseppe Campiani、Sandra Gemma

  DOI：10.1021/jm501119j

  日期：2014.11.26

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.
• Synthesis of benzo-fused, 7,5- and 7,6-fused azepinones as conformationally restricted dipeptide mimetics
  作者：Jeffrey A. Robl、Donald S. Karanewsky、Magdi M. Asaad

  DOI：10.1016/0040-4039(95)00096-u

  日期：1995.3

  generation of novel conformationally restricted dipeptide mimetics 9 and 16 has been developed. The key step involved intramolecular addition of an oxonium ion to the proximal indoline/tetrahydroquinoline aromatic ring. A dramatic difference in reactivity was observed in the formation of the 7,5- versus the 7,6-fused azepinone nuclei. Application of these mimetics in the synthesis of dual-acting ACE/NEP

  已经开发了用于产生新的构象受限的二肽模拟物9和16的方法。关键步骤涉及在近端二氢吲哚/四氢喹啉芳族环中分子内添加氧鎓离子。在7，5-与7，6-融合的氮杂pin酮核的形成中观察到反应性的显着差异。描述了这些模拟物在合成双作用ACE / NEP抑制剂1和2中的应用。