7-(4-bromobutoxy)-8-chloro-4-methyl-2H-chromen-2-one | 1440946-57-5

• 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-(4-bromobutoxy)-8-chloro-4-methyl-2H-chromen-2-one
• CAS: 1440946-57-5
• 化学式: C₁₄H₁₄BrClO₃
• 分子量: 345.62
• InChiKey: WGXCCUANJVWUSQ-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107 °C
• 沸点：
  478.5±45.0 °C(predicted)
• 密度：
  1.478±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  39.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2-甲氧苯基)哌嗪 、 7-(4-bromobutoxy)-8-chloro-4-methyl-2H-chromen-2-one 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 以70.1%的产率得到7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-4-methyl-8-chloro-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
• 作为产物：
  描述：

  2-氯-1,3-苯二酚 在 硫酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 7-(4-bromobutoxy)-8-chloro-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

• Privileged scaffold-based design to identify a novel drug-like 5-HT7 receptor-preferring agonist to target Fragile X syndrome
  作者：Enza Lacivita、Mauro Niso、Madia Letizia Stama、Anna Arzuaga、Concetta Altamura、Lara Costa、Jean-François Desaphy、Michael E. Ragozzino、Lucia Ciranna、Marcello Leopoldo

  DOI：10.1016/j.ejmech.2020.112395

  日期：2020.8

  in preclinical candidates (privileged scaffolds). The new compounds were synthesized, tested for their affinity at 5-HT7 and 5-HT1A receptors, and screened for their in vitro stability to microsomal degradation and toxicity. Selected compounds were characterized as 5-HT7 receptor-preferring ligands, endowed with high metabolic stability and low toxicity. Compound 7g emerged as a drug-like 5-HT7 receptor-preferring

  最近的临床前研究表明，血清素5-HT7受体的激活具有治疗神经发育障碍（如脆弱X综合征）的潜力，脆弱X综合征是一种以自闭症为特征的罕见疾病。为了向科学界提供多样化的药物样5-HT7受体优先激动剂，我们通过利用临床批准药物或临床前候选药物（特权支架）中存在的结构片段设计了一组新的长链芳基哌嗪。合成了这些新化合物，测试了它们对5-HT7和5-HT1A受体的亲和力，并筛选了它们对微粒体降解和毒性的体外稳定性。所选择的化合物被表征为5-HT7受体优选的配体，具有高代谢稳定性和低毒性。