N-(4-(4-phenylpiperazin-1-yl)butyl)quinoline-6-carboxamide | 1020092-54-9

• 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: N-(4-(4-phenylpiperazin-1-yl)butyl)quinoline-6-carboxamide
• 英文别名: N-[4-(4-phenylpiperazin-1-yl)butyl]quinoline-6-carboxamide
• CAS: 1020092-54-9
• 化学式: C₂₄H₂₈N₄O
• 分子量: 388.513
• InChiKey: OURPZJJZFFKVJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-甲基喹啉 在 chromium(VI) oxide 、 四溴化碳 、 硫酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 48.0h， 生成 N-(4-(4-phenylpiperazin-1-yl)butyl)quinoline-6-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

文献信息

• ARYL PIPERAZINE DERIVATIVES USEFUL FOR THE TREATMENT OF NEUROPSYCHIATRY DISORDERS
  申请人：Campiani Giuseppe

  公开号：US20100087445A1

  公开（公告）日：2010-04-08

  This invention provides novel aryl piperazine derivatives represented by Formula (I) having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D 3 , 5HT 1A and 5-HT 2A receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders, incl. schizophrenia.

  本发明提供了具有医疗用途的新型芳基哌嗪衍生物，其化学式表示为（I），特别是作为多巴胺和血清素受体的调节剂，优选D3、5HT1A和5-HT2A受体亚型，特别适用于治疗神经精神疾病，包括精神分裂症。
• WO2008/43839
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.