7-(4-(4-(4-methoxyphenyl)piperazin-1-yl)butoxy)-4-methyl-2H-chromen-2-one | 1314133-68-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 7-(4-(4-(4-methoxyphenyl)piperazin-1-yl)butoxy)-4-methyl-2H-chromen-2-one
• 英文别名: 7-[4-[4-(4-Methoxyphenyl)piperazin-1-yl]butoxy]-4-methylchromen-2-one；7-[4-[4-(4-methoxyphenyl)piperazin-1-yl]butoxy]-4-methylchromen-2-one
• CAS: 1314133-68-0
• 化学式: C₂₅H₃₀N₂O₄
• 分子量: 422.524
• InChiKey: RAGAEQXVBSYFOF-UHFFFAOYSA-N

物化性质

• 熔点：
  108-109 °C
• 沸点：
  604.8±55.0 °C(predicted)
• 密度：
  1.169±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  羟甲香豆素 在 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 48.0h， 生成 7-(4-(4-(4-methoxyphenyl)piperazin-1-yl)butoxy)-4-methyl-2H-chromen-2-one
  参考文献：
  名称：

  香豆素衍生物作为α1-肾上腺素受体拮抗剂的合理设计，合成，生物学评估，同源性和对接研究。

  摘要：

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。

  DOI：

  10.1002/cbdv.201000135

文献信息

• 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.
• Rational Design, Synthesis, Biological Evaluation, Homology and Docking Studies of Coumarin Derivatives as α1-Adrenoceptor Antagonists
  作者：Xiang Zhou、Ya-Dong Chen、Tao Wang、Xiao-Bing Wang、Ling-Yi Kong

  DOI：10.1002/cbdv.201000135

  日期：2011.6

  -adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α(1) -AR. These synthesized coumarin derivatives exhibited high efficacies towards α(1) -AR in in vitro pharmacological assays. Compared with prazosin (pK(i) value of 8.77), among those coumarins, tolylpiperazine-substituted derivatives, 7 and 8

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。