7-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)-4-methyl-2H-chromen-2-one | 1338325-73-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)-4-methyl-2H-chromen-2-one
• 英文别名: 7-(3-(4-(3-(6-fluorobenzisoxazole)-1-piperidyl)-2-hydroxylpropoxy))-4-methyl-2H-benzopyran-2-one；7-(3-(4-(6-fluorobenzoisoxazol-3-yl)-1-piperidyl)-2-hydroxypropoxy)-4-methyl-2H-benzopyran-2-one；7-[3-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]-2-hydroxypropoxy]-4-methylchromen-2-one
• CAS: 1338325-73-7
• 化学式: C₂₅H₂₅FN₂O₅
• 分子量: 452.482
• InChiKey: LAFPJOIXDXNYEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  85
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  羟甲香豆素 在 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 7-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)-4-methyl-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis and Biological Investigation of Coumarin Piperazine (Piperidine) Derivatives as Potential Multireceptor Atypical Antipsychotics

  摘要：

  The discovery and synthesis of potential and novel antipsychotic coumarin derivatives, associated with potent dopamine 132, D3, and serotonin S-HT1A and S-HT2A, receptor properties, are the focus of the present article. The most-promising derivative was 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro-2H- chromen-2-one (17m). This derivative possesses unique pharmacological features, including high affinity for dopamine D-2 and D-3 and serotonin S-HT1A and 5-HT2A receptors. Moreover, it possesses low affinity for S-HT2C and H-1 receptors (to reduce the risk of obesity associated with chronic treatment) and hERG channels (to reduce the incidence of torsade des pointes). In animal models, compound 17m inhibited apomorphine-induced climbing behavior, MK-801-induced hyperactivity, and the conditioned avoidance response without observable catalepsy at the highest dose tested. Further, fewer preclinical adverse events were noted with 17m compared with risperidone in assays that measured prolactin secretion and weight gain. Acceptable pharmacokinetic properties were also noted with 17m. Taken together, 17m may constitute a novel class of drugs for the treatment of schizophrenia.

  DOI：

  10.1021/jm400408r

文献信息

• BENZOPYRONE DERIVATIVE AND USE THEREOF
  申请人：Huazhong University of Science and Technology

  公开号：EP2698369B1

  公开（公告）日：2017-02-01
• US9315496B2
  申请人：——

  公开号：US9315496B2

  公开（公告）日：2016-04-19
• Synthesis and Biological Investigation of Coumarin Piperazine (Piperidine) Derivatives as Potential Multireceptor Atypical Antipsychotics
  作者：Yin Chen、Songlin Wang、Xiangqing Xu、Xin Liu、Minquan Yu、Song Zhao、Shicheng Liu、Yinli Qiu、Tan Zhang、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/jm400408r

  日期：2013.6.13

  The discovery and synthesis of potential and novel antipsychotic coumarin derivatives, associated with potent dopamine 132, D3, and serotonin S-HT1A and S-HT2A, receptor properties, are the focus of the present article. The most-promising derivative was 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro-2H- chromen-2-one (17m). This derivative possesses unique pharmacological features, including high affinity for dopamine D-2 and D-3 and serotonin S-HT1A and 5-HT2A receptors. Moreover, it possesses low affinity for S-HT2C and H-1 receptors (to reduce the risk of obesity associated with chronic treatment) and hERG channels (to reduce the incidence of torsade des pointes). In animal models, compound 17m inhibited apomorphine-induced climbing behavior, MK-801-induced hyperactivity, and the conditioned avoidance response without observable catalepsy at the highest dose tested. Further, fewer preclinical adverse events were noted with 17m compared with risperidone in assays that measured prolactin secretion and weight gain. Acceptable pharmacokinetic properties were also noted with 17m. Taken together, 17m may constitute a novel class of drugs for the treatment of schizophrenia.