2-(4-(dimethylamino)benzylidene)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one | 1025637-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(4-(dimethylamino)benzylidene)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one
• 英文别名: 2-[1-(4-dimethylaminophenyl)methylidene]-5,6-dimethoxyindan-1-one；2-[[4-(dimethylamino)phenyl]methylidene]-5,6-dimethoxy-3H-inden-1-one
• CAS: 1025637-00-6
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: HDVCLPMRJWHUAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对氟苯甲醛 在 四丁基溴化铵 、 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 2-(4-(dimethylamino)benzylidene)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  Multitarget-Directed Benzylideneindanone Derivatives: Anti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer’s Disease

  摘要：

  A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced beta-amyloid (A beta(1-42)) aggregation (10.5-80.1%, 20 mu M) and MAO-B activity (IC50 of 7.5-40.5 mu M), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit A beta(1-42) aggregation (80.1%), and MAO-B (IC50 = 7.5 mu M) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced A beta(1-42) aggregation and disassembling the well-structured A beta fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.

  DOI：

  10.1021/jm300978h

文献信息

• Synthesis, biological evaluation and 3D-QSAR studies of new chalcone derivatives as inhibitors of human P-glycoprotein
  作者：Zahida Parveen、Gerda Brunhofer、Ishrat Jabeen、Thomas Erker、Peter Chiba、Gerhard F. Ecker

  DOI：10.1016/j.bmc.2014.02.005

  日期：2014.4

  one order of magnitude higher than the activity for an equilipohillic propafenone analogue. 2D- and 3D-QSAR studies indicate the importance of H-bond acceptors, methoxy groups, hydrophobic groups as well as the number of rotatable bonds as pharmacophoric features influencing P-gp inhibitory activity.

  P-糖蛋白（P-gp）是一种依赖ATP的多药耐药外排转运蛋白，在抗癌药物耐药和药物药代动力学中起重要作用。尽管有大量结构和功能多样的化合物，但黄酮类化合物和查耳酮也被报道为 P-gp 的抑制剂。后者与经过充分研究的普罗帕酮类有一些相似之处，但不含碱性氮原子。此外，由于它们的刚性，它们是 3D-QSAR 研究的合适候选者。在这项研究中，合成了一组 22 种新的查尔酮衍生物，并在使用 CCRF.CEM.VCR1000 细胞系的道诺霉素流出抑制试验中进行了评估。化合物10显示出最高的活性 (IC 50 = 42 nM)，比等脂亲普罗帕酮类似物的活性高一个数量级。2D 和 3D-QSAR 研究表明 H 键受体、甲氧基、疏水基团以及可旋转键的数量作为影响 P-gp 抑制活性的药效团特征的重要性。
• Multifunctional indanone–chalcone hybrid compounds with anti-β-amyloid (Aβ) aggregation, monoamine oxidase B (MAO-B) inhibition and neuroprotective properties against Alzheimer’s disease
  作者：Keren Wang、Lintao Yu、Jian Shi、Wenmin Liu、Zhipei Sang

  DOI：10.1007/s00044-019-02423-4

  日期：2019.11

  discover multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of indanone–chalcone hybrid compounds were designed and synthesized based on the multitarget-directed ligand strategy. Their monoamino oxidases (MAO-A and MAO-B) and Aβ1–42 aggregation inhibitory activities were evaluated. The results were shown that all synthetic compounds exhibited mostly good multifunctional activities

  为了发现用于治疗阿尔茨海默氏病（AD）的多功能药物，基于多靶标定向配体策略设计并合成了一系列茚满酮-查尔酮杂化化合物。评估了它们的单氨基氧化酶（MAO-A和MAO-B）和Aβ1–42聚集抑制活性。结果表明，所有合成化合物均表现出良好的多功能活性。它们之中，化合物TM-11表示的最好的甲β 1-42聚集抑制效力（IC 50  〜1.8μM）和良好的解聚作用的活性（IC 50  〜7.9微米）。TEM图像和对接研究都为该假设提供了良好的合理解释。同时，化合物TM-11是一种选择性MAO-B抑制剂，以及针对A中的神经保护剂β 1-42诱导的毒性。基于结构上的考虑，化合物TM-11的亲脂性可根据Lipinski的5法则在体外穿过血脑屏障（BBB）。总之，这些结果表明，化合物TM-11可能是治疗AD的潜在多功能剂。