(±)-11-amino-10-(3-(3,4-dimethoxyphenyl)-8-isopropyl-2-oxo-2H-chromen-6-yl)-7,7-dimethyl-2,3,6,7,8,10-hexahydrochromeno[2,3-b]cyclopenta[e]pyridin-9(1H)-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: (±)-11-amino-10-(3-(3,4-dimethoxyphenyl)-8-isopropyl-2-oxo-2H-chromen-6-yl)-7,7-dimethyl-2,3,6,7,8,10-hexahydrochromeno[2,3-b]cyclopenta[e]pyridin-9(1H)-one
• 英文别名: 11-Amino-9-[3-(3,4-dimethoxyphenyl)-2-oxo-8-propan-2-ylchromen-6-yl]-5,5-dimethyl-2-oxa-17-azatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),3(8),10,12(16)-tetraen-7-one；11-amino-9-[3-(3,4-dimethoxyphenyl)-2-oxo-8-propan-2-ylchromen-6-yl]-5,5-dimethyl-2-oxa-17-azatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),3(8),10,12(16)-tetraen-7-one
• 化学式: C₃₇H₃₈N₂O₆
• 分子量: 606.719
• InChiKey: WKIUXCZTYUHFNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  45
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  异丙苯酚 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 aluminum (III) chloride 、 三聚氯氰 、 三乙胺 作用下， 以 乙醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.92h， 生成 (±)-11-amino-10-(3-(3,4-dimethoxyphenyl)-8-isopropyl-2-oxo-2H-chromen-6-yl)-7,7-dimethyl-2,3,6,7,8,10-hexahydrochromeno[2,3-b]cyclopenta[e]pyridin-9(1H)-one
  参考文献：
  名称：

  Discovery of 3-Arylcoumarin-tetracyclic Tacrine Hybrids as Multifunctional Agents against Parkinson’s Disease

  摘要：

  A series of multifunctional directed 3-arylcoumarin-tetracyclic tacrine derivatives was designed and synthesized for the treatment of Parkinson's disease (PD). A number of derivatives (18, 19, 20, 21, and 24) demonstrated significant reduction of aggregation of "human" alphasynuclein (a-synuclein) protein, expressing on transgenic Caenorhabditis elegans (C. elegans) model NL5901. Moreover, compounds 16, 18, and 24 also exhibited good antioxidant properties and significantly increased the dopamine (DA) content in N2 and NL5901 strains of C. elegans. Interestingly, the protective efficacy of these hybrids seems to be mediated via activation of longevity promoting transcription factor DAF-16. In addition, molecular modeling studies have evidenced the exquisite interaction of most active compounds 18 and 24 with asynuclein protein. Taken together, the data indicate that the derivatives may be useful leads against aging and age associated PD.

  DOI：

  10.1021/ml500222g

文献信息

• Discovery of 3-Arylcoumarin-tetracyclic Tacrine Hybrids as Multifunctional Agents against Parkinson’s Disease
  作者：Koneni V. Sashidhara、Ram K. Modukuri、Pooja Jadiya、K. Bhaskara Rao、Tanuj Sharma、Rizwanul Haque、Deependra Kumar Singh、Dibyendu Banerjee、Mohammad Imran Siddiqi、Aamir Nazir

  DOI：10.1021/ml500222g

  日期：2014.10.9

  A series of multifunctional directed 3-arylcoumarin-tetracyclic tacrine derivatives was designed and synthesized for the treatment of Parkinson's disease (PD). A number of derivatives (18, 19, 20, 21, and 24) demonstrated significant reduction of aggregation of "human" alphasynuclein (a-synuclein) protein, expressing on transgenic Caenorhabditis elegans (C. elegans) model NL5901. Moreover, compounds 16, 18, and 24 also exhibited good antioxidant properties and significantly increased the dopamine (DA) content in N2 and NL5901 strains of C. elegans. Interestingly, the protective efficacy of these hybrids seems to be mediated via activation of longevity promoting transcription factor DAF-16. In addition, molecular modeling studies have evidenced the exquisite interaction of most active compounds 18 and 24 with asynuclein protein. Taken together, the data indicate that the derivatives may be useful leads against aging and age associated PD.