1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1-one | 203058-56-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1-one
• 英文别名: 1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethan-1-one；1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-ethanone；1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethanone
• CAS: 203058-56-4
• 化学式: C₁₈H₂₀O₅
• mdl: MFCD28404507
• 分子量: 316.354
• InChiKey: FUSFENWZOPWHAL-UHFFFAOYSA-N

物化性质

• 沸点：
  464.9±40.0 °C(Predicted)
• 密度：
  1.139±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1-one 在 溴 作用下， 以 乙醚 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of diarylthiazole derivatives as antimitotic and antivascular agents with potent antitumor activity

  摘要：

  By switching position of the N and S atom in the thiazole ring which were similar to the previously reported agent 5-(4-ethoxyphenyl)-4-(3',4',5'-trimethoxyphenyl)thiazol-2-amine, a series of 4,5-diarylthiazole derivatives were synthesized using Friedel-Crafts reaction based on chemical modification of Combrestatatin A-4 (CA-4). Their antiproliferative activities were evaluated and identified as new microtubule destabilizing agents. Structure-activity relationship study indicated that compound 8a with 3,4,5-trimethoxyphenyl group at the C-4 position and 4-ethoxyphenyl group at the C-5 position of 2-amino substituted thiazole was of the most potent inhibitory activity in this series. 8a was found to exhibit the IC50 values of 8.4-26.4 nM in five human cancer cell lines, with comparable inhibition effects to CA-4. Moreover, 8a showed potency as a tubulin polymerization inhibitor, with colchicine site binding ability and comparable extent of inhibition against the growth of P-glycoprotein over-expressing multidrug resistant cell lines. Mechanism studies revealed that 8a could block the progression of cell cycle in the G2/M phase and result in cellular apoptosis in cancer cells. As a new tubulin destabilizing agent, 8a was also found high antivascular activity as it concentration-dependently reduced the cell migration and disrupted capillary like tube formation of HUVEC cells. Furthermore, 8a significantly suppressed the tumor growth in HCT116 and SK-OV-3 xenograft models with tumor growth inhibitory rate of 55.12% and 72.7%, respectively. Our studies highlighted that 8a was a promising microtubule targeting antitumor agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.055
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 aluminum (III) chloride 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of diarylthiazole derivatives as antimitotic and antivascular agents with potent antitumor activity

  摘要：

  By switching position of the N and S atom in the thiazole ring which were similar to the previously reported agent 5-(4-ethoxyphenyl)-4-(3',4',5'-trimethoxyphenyl)thiazol-2-amine, a series of 4,5-diarylthiazole derivatives were synthesized using Friedel-Crafts reaction based on chemical modification of Combrestatatin A-4 (CA-4). Their antiproliferative activities were evaluated and identified as new microtubule destabilizing agents. Structure-activity relationship study indicated that compound 8a with 3,4,5-trimethoxyphenyl group at the C-4 position and 4-ethoxyphenyl group at the C-5 position of 2-amino substituted thiazole was of the most potent inhibitory activity in this series. 8a was found to exhibit the IC50 values of 8.4-26.4 nM in five human cancer cell lines, with comparable inhibition effects to CA-4. Moreover, 8a showed potency as a tubulin polymerization inhibitor, with colchicine site binding ability and comparable extent of inhibition against the growth of P-glycoprotein over-expressing multidrug resistant cell lines. Mechanism studies revealed that 8a could block the progression of cell cycle in the G2/M phase and result in cellular apoptosis in cancer cells. As a new tubulin destabilizing agent, 8a was also found high antivascular activity as it concentration-dependently reduced the cell migration and disrupted capillary like tube formation of HUVEC cells. Furthermore, 8a significantly suppressed the tumor growth in HCT116 and SK-OV-3 xenograft models with tumor growth inhibitory rate of 55.12% and 72.7%, respectively. Our studies highlighted that 8a was a promising microtubule targeting antitumor agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.055

文献信息

• Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents
  作者：Marina N. Semenova、Dmitry V. Demchuk、Dmitry V. Tsyganov、Natalia B. Chernysheva、Alexander V. Samet、Eugenia A. Silyanova、Victor P. Kislyi、Anna S. Maksimenko、Alexander E. Varakutin、Leonid D. Konyushkin、Mikhail M. Raihstat、Alex S. Kiselyov、Victor V. Semenov

  DOI：10.1021/acscombsci.8b00113

  日期：2018.12.10

  antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure–activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively

  通过改进的方案合成了一系列新颖的和已报道的康布雷他汀类似物，包括二芳基吡唑，-异恶唑，-1,2,3-三唑和-吡咯，以使用体内海胆胚胎测定法和专家小组评估其抗有丝分裂的抗微管蛋白活性。人类癌细胞 对这些化合物进行了系统的比较结构-活性关系研究。吡唑1i和1p，异恶唑3a和三唑7b被发现是所有测试化合物中最有效的抗有丝分裂剂，分别导致海胆胚胎的裂解改变分别为1、0.25、1和0.5 nM。这些试剂对人癌细胞显示出可比的细胞毒性。结构-活性关系研究表明，被3,4,5-三甲氧基苯基环A和4-甲氧基苯基环B取代的化合物表现出最高的活性。B环中的3-羟基对于二芳基异恶唑系列的抗增殖活性至关重要，而对二芳基吡唑的效力则不是必需的。具有3,4,5-三甲氧基取代的环A和3-羟基-4-甲氧基取代的环B的异恶唑3比各自的吡唑1具有更高的活性。与同一组的其他芳药效团取代的唑类，二芳基的1，4,5- diarylisoxazoles
• p-Toluenesulfonic acid-promoted selective functionalization of unsymmetrical arylalkynes: a regioselective access to various arylketones and heterocycles
  作者：Maud Jacubert、Olivier Provot、Jean-François Peyrat、Abdallah Hamze、Jean-Daniel Brion、Mouâd Alami

  DOI：10.1016/j.tet.2010.03.055

  日期：2010.5

  Regioselective hydration of a wide range of internal alkynes has been afforded in high to good yields by using PTSA in EtOH. The scope of the reaction of alkynes has been delineated. Arylaliphatic alkynes and diarylalkynes were regioselectively hydrated in good to excellent yields and short reaction times when the reaction was achieved under microwave irradiation. Moreover, diarylalkynes, arylenynes

  通过在EtOH中使用PTSA，可以实现高产率到良好产率的多种内部炔烃的区域选择性水合。已经描述了炔烃的反应范围。当在微波辐射下完成反应时，芳基脂族炔烃和二芳基炔烃以良好至优异的产率和短的反应时间进行区域选择性水合。而且，对在邻位带有甲氧基或硫代甲基取代基的二芳基炔，芳炔和二芳基二炔进行区域选择性5-内酯化。-dig-环化得到各种2-芳基-和2-苯乙烯基苯并呋喃或苯并噻吩衍生物。我们相信，这种新的无金属污染的环保方法与微波辐射相结合，对于绿色实验室规模的合成研究将非常重要。
• A Simple Method for the Synthesis of Substituted Benzylic Ketones:  Homologation of Aldehydes via the in Situ Generation of Aryldiazomethanes from Aromatic Aldehydes
  作者：Steven R. Angle、Martin L. Neitzel

  DOI：10.1021/jo000446y

  日期：2000.10.1

  A general method for the homologation of aldehydes to benzylic ketones has been developed. Aryldiazomethanes were generated in situ in the presence of an aldehyde by simply heating the tosylhydrazones of aromatic aldehydes in the presence of a stoichiometric amount of base in polar protic solvents. The resulting polar protic solvent promoted homologation afforded benzylic ketones in moderate to excellent

  已经开发了将醛同源化为苄基酮的通用方法。芳族重氮甲烷是在醛存在下，通过在极性化学溶剂中，在化学计量的碱存在下，简单加热芳族醛的甲苯磺酰hydr生成的。所得的极性质子溶剂促进的同源性提供了具有各种醛的中等至极好的收率的苄基酮。不需要分离甲苯磺酰hydr；它们可以在乙醇中制备，无需分离即可完成整个序列。这种方法学使人们可以轻松获得各种困难甚至不可能的取代芳基重氮甲烷。
• 一种氟取代二苯乙烷类化合物及制备方法和 应用
  申请人：上海应用技术大学

  公开号：CN110240539B

  公开（公告）日：2021-12-07

  本发明涉及一种氟取代二苯乙烷类化合物，其特征在于，其结构如通式(Ⅰ)：其中：R1为甲基或乙基；R2为氢或氟；R为氢、羟基、苄氧基、磷酸酯、磷酸酯盐。与现有技术相比，本发明在二苯乙烷的桥键进行氟取代修饰，所得到的氟代二苯乙烷衍生物具有较强的体外抗肿瘤活性，氟原子的引入改变了化合物的物理、化学和生物性质，对肿瘤细胞具有明显的抑制作用；制备条件简便易行，副产物较少。
• Synthesis and biological evaluation of 2,3-diarylthiophene analogues of combretastatin A-4
  作者：Zhan Wang、Qingkun Yang、Zhaoshi Bai、Jun Sun、Xuewei Jiang、Hongrui Song、Yingliang Wu、Weige Zhang

  DOI：10.1039/c5md00028a

  日期：——

  A series of novel 2,3-diarylthiophene analogues of combretastatin A-4 were synthesised and evaluated for their in vitro anti-proliferative activities.

  一系列新型的2,3-二芳基噻吩衍生物（类似于连马菜素A-4）被合成并评估其体外抗增殖活性。