N-[4-羟基-3-(1-氧代-3-苯基烯丙基)苯基]乙酰胺 | 24449-58-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 中文名称: N-[4-羟基-3-(1-氧代-3-苯基烯丙基)苯基]乙酰胺
• 中文别名: 3,6-亚甲基呋喃并[2,3-d][1,6,2]二噁吖辛因(9CI)
• 英文名称: 5'-Acetamino-2'-hydroxy-chalkon
• 英文别名: N-(4-Hydroxy-3-(1-oxo-3-phenylallyl)phenyl)acetamide；N-[4-hydroxy-3-(3-phenylprop-2-enoyl)phenyl]acetamide
• CAS: 24449-58-9
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: PQOXQUOIPRIKBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  N-[4-羟基-3-(1-氧代-3-苯基烯丙基)苯基]乙酰胺 在 吡啶 、 盐酸 、 水 、 碘 作用下， 以 二甲基亚砜 为溶剂， 反应 7.0h， 生成 4-benzylidene-1-(4-oxo-2-phenyl-4H-chromen-6-yl)-2-phenyl-1H-imidazol-5-one
  参考文献：
  名称：

  Synthesis and evaluation of a series of novel imidazolidinone analogues of 6-aminoflavone as anticancer and anti-inflammatory agents

  摘要：

  The flavone moiety is a potential pharmacophore known for its diverse range of pharmacological activities. Aminoflavones have recently been the subject of considerable attention as lead molecules in several cancer research projects. Imidazolidinone heterocycles represent another biologically active scaffold with known cytotoxic properties. In an attempt to provide synergistic cytotoxic activity, these two moieties have been combined, and the resulting novel analogues evaluated for their anticancer and anti-inflammatory activities. The results revealed that the cytotoxicities of these compounds were fivefold greater than those of aminoflavone. DNA histograms obtained from cell cycle analysis in the presence of these compounds were apoptotic in their nature. Furthermore, the in vivo screening of these compounds using Ehrlich's ascites tumour model showed an increase in life span, whereas an in vivo anti-inflammatory study resulted in the enhancement of the anti-inflammatory potential. The results therefore supported the hypothesis that there is a relationship between inflammation and cancer.

  DOI：

  10.1007/s00044-013-0486-7
• 作为产物：
  描述：

  对乙酰氨基酚 在 aluminum (III) chloride 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 硝基苯 为溶剂， 反应 15.5h， 生成 N-[4-羟基-3-(1-氧代-3-苯基烯丙基)苯基]乙酰胺
  参考文献：
  名称：

  Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6-Aminoflavone

  摘要：

  通过将黄酮核与噻唑烷二酮环结合，合成了一系列新型杂环类似物，旨在增强黄酮已知的抗癌活性。合成了6-氨基黄酮、6-氨基-3-甲氧基黄酮、6-氨基-3-甲氧基-3′，4′-二甲氧基黄酮及其相应的噻唑烷二酮类似物。合成了十五种新型类似物，并通过基于细胞的检测技术和小鼠体内的癌症检测试验，评估了它们的抗癌活性。如预期的，这些类似物提高了细胞毒性，并显示出能延长携癌小鼠的寿命。细胞毒性评估使用了3-(4,5-二甲基噻唑-2-基)-2, 5-二苯基四唑溴盐（MTT）法在HeLa，MDA-MB-435和Vero细胞系上进行。在患有Dalton腹水癌的白色小鼠中的体内抗癌活性评价表明，这些新类似物延长了生命周期并阻止了肿瘤体积导致的体重增加。此外，细胞周期分析和Hoechst染色分析证明了这些类似物的凋亡潜力。对合成的化合物进行了初步的药代动力学评价，以确定其亲脂性和pKa。通过高效液相色谱法确定亲脂性，结果显示出观察到的抗癌活性和log P值之间的直接关联，而pKa值指示了电离范围，这是预测溶解度和渗透性的工具。

  DOI：

  10.1248/cpb.c15-00454

文献信息

• Synthesis and complete assignment of the 1H and 13C NMR signals of new acetamido and aminoflavonoid derivatives
  作者：Gilles Casano、Maxime Robin、Pascale Barbier、Vincent Peyrot、Robert Faure

  DOI：10.1002/mrc.2638

  日期：2010.9

  The complete 1H and 13C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamidoflavonols and 9 aminoflavonols has been performed using one‐ and two‐dimensional NMR techniques including COSY, HMQC and HMBC experiments. Copyright © 2010 John Wiley & Sons, Ltd.

  已使用包括 COSY、HMQC 和 HMBC 实验在内的一维和二维 NMR 技术对 9 种乙酰氨基查耳酮、18 种乙酰氨基黄酮、18 种氨基黄酮、9 种乙酰氨基黄酮醇和 9 种氨基黄酮醇进行了完整的 1H 和 13C NMR 归属。版权所有 © 2010 John Wiley & Sons, Ltd.
• Flavonols
  申请人：The University of Melbourne

  公开号：US07863323B1

  公开（公告）日：2011-01-04

  A compound of the formula (I): wherein R is selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl and acyl, each of which may be optionally substituted; R1 is an organic moiety that is capable of being converted into a charged group; each X and Y is independently selected from the group consisting of H, halogen, —CN, —NO2, —CF3, —OCF3, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, arylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, arylalkyloxy, phenoxy, benzyloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —COOH, —COR2, —COOR2, —CONHR2, —NHCOR2, —NHCOOR2, —NHCONHR2, C(═NOH)R2, alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, SR2 and acyl, each of which may be optionally substituted; each R2 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, and acyl, each of which may be optionally substituted; m is an integer selected from the group consisting of 0, 1, 2, 3, 4 and 5; p is an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or prodrug thereof.

  公式（I）的化合物：其中R从H、烷基、烯基、炔基、杂原子烷基、环烷基、杂环烷基、芳基、杂芳基和酰基组成的群中选择，每个都可以选择性地被取代；R1是一个有能力转化为带电基团的有机基团；每个X和Y分别从H、卤素、—CN、—NO2、—CF3、—O 、烷基、烯基、炔基、卤代烷基、卤代烯基、杂原子烷基、环烷基、环烯基、杂环烷基、杂环烯基、芳基、杂芳基、环烷基烷基、杂环烷基烷基、芳基烷基、杂芳基烷基、芳基烯基、环烷基杂原子烷基、芳基杂原子烷基、杂环烷基杂原子烷基、杂芳基杂原子烷基、羟基、羟基烷基、烷氧基、烷氧基烷基、烷氧基芳基、烯基氧基、炔基氧基、环烷氧基、杂环烷氧基、芳氧基、杂芳氧基、芳基烷氧基、苯氧基、苄氧基、氨基、烷基氨基、氨基烷基、酰氨基、芳基氨基、磺酰氨基、亚砜氨基、—COOH、—COR2、—COOR2、—CONHR2、—NHCOR2、—NHCOOR2、—NHCONHR2、C(═NOH)R2、烷氧羰基、烷基氨基羰基、磺酰基、烷基磺酰基、烷基亚砜基、芳基磺酰基、芳基亚砜基、氨基磺酰基、SR2和酰基组成的群中选择，每个都可以选择性地被取代；每个R2从H、烷基、烯基、炔基、卤代烷基、杂原子烷基、环烷基、杂环烷基、芳基、杂芳基、环烷基烷基、杂环烷基烷基、芳基烷基、杂芳基烷基和酰基组成的群中选择，每个都可以选择性地被取代；m是从0、1、2、3、4和5中选择的整数；p是从0、1、2和3中选择的整数；或其药用盐或前药。
• 2-Aminothiazole-Flavonoid Hybrid Derivatives Binding to Tau Protein and Responsible for Antitumor Activity in Glioblastoma
  作者：Rayane Hedna、Attilio DiMaio、Maxime Robin、Diane Allegro、Mario Tatoni、Vincent Peyrot、Pascale Barbier、Hervé Kovacic、Gilles Breuzard

  DOI：10.3390/ijms242015050

  日期：——

  Tau protein has been described for several decades as a promoter of tubulin assembly into microtubules. Dysregulation or alterations in Tau expression have been related to various brain cancers, including the highly aggressive and lethal brain tumor glioblastoma multiform (GBM). In this respect, Tau holds significant promise as a target for the development of novel therapies. Here, we examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau binding, Tau fibrillation, and cellular effects on Tau-expressing cancer cells. By spectrofluorometric approach, we found that two compounds, 2 and 9, demonstrated high affinity for Tau and exhibited a strong propensity to inhibit Tau fibrillation. Then, the biological activity of these compounds was evaluated on several Tau-expressing cells derived from glioblastoma. The two lead compounds displayed a high anti-metabolic activity on cells related to an increased fission of the mitochondria network. Moreover, we showed that both compounds induced microtubule bundling within newly formed neurite-like protrusions, as well as with defection of cell migration. Taken together, our results provide a strong experimental basis to develop new potent molecules targeting Tau-expressing cancer cells, such as GBM.

  几十年来，Tau 蛋白一直被描述为促进微管蛋白组装成微管的因子。Tau 蛋白表达的失调或改变与多种脑癌有关，包括侵袭性和致死性极强的多形性胶质母细胞瘤（GBM）。因此，Tau 很有希望成为开发新型疗法的靶点。在这里，我们研究了17种新系列的2-氨基噻唑与类黄酮融合的杂化化合物（TZF）在Tau结合、Tau纤维化以及对表达Tau的癌细胞的细胞效应方面的结构-活性关系。通过光谱荧光测定法，我们发现 2 和 9 这两种化合物与 Tau 的亲和力很高，并表现出强烈的抑制 Tau 纤维化的倾向。随后，我们对这些化合物在几种来自胶质母细胞瘤的 Tau 表达细胞上的生物活性进行了评估。这两种先导化合物对细胞具有很高的抗代谢活性，这与线粒体网络裂变增加有关。此外，我们还发现这两种化合物都能诱导新形成的神经元样突起内的微管成束，并使细胞迁移发生缺陷。综上所述，我们的研究结果为开发针对 Tau 表达癌细胞（如脑胶质瘤）的新型强效分子提供了坚实的实验基础。
• Kunckell, Chemische Berichte, 1904, vol. 37, p. 2826
  作者：Kunckell

  DOI：——

  日期：——
• Studies in Chalcones and Related Compounds Derived from 2-Hydroxy-5-acetaminoacetophenone: Part I. Synthesis of 2-Hydroxy-5′-acetaminochalcones and 6-Aminoflavanones
  作者：A. A. RAVAL、N. M. SHAH

  DOI：10.1021/jo01118a021

  日期：1956.12.1