1-(3’,4,’5’-trimethoxyphenyl)-3-[4-(N,N-dimethylaminophenyl)]-prop-2-enone | 119261-19-7

• 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
• 英文名称: 1-(3’,4,’5’-trimethoxyphenyl)-3-[4-(N,N-dimethylaminophenyl)]-prop-2-enone
• 英文别名: 3-[4-(Dimethylamino)phenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 119261-19-7
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: UVWVWBTZPMIHCN-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C
• 沸点：
  522.2±50.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3’,4,’5’-trimethoxyphenyl)-3-[4-(N,N-dimethylaminophenyl)]-prop-2-enone 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以92%的产率得到5-[4-(dimethylamino)phenyl]-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole
  参考文献：
  名称：

  Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives

  摘要：

  A series of 3,5-diaryl-4,5-dihydropyrazole regioisomers, and their 1-acetylated derivatives, bearing a 3,4,5-trimethoxyphenyl moiety combined with a variety of substituted phenyl rings, was synthesized and evaluated for antitumor activity. Results of the in vitro assay against a non-small cell lung carcinoma cell line (NCI-H460) showed several compounds to be endowed with cytotoxicity in micromolar to sub-micromolar range, depending on substitution pattern and position of aryl rings on 4,5-dihydropyrazole core. Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. 5-(3,4,5-Trimethoxyphenyl) pyrazolines 31 and 39 were found to possess potent antiproliferative activity against SR and MDA-MB-435, with GI(50) inhibitory values in nanomolar range. Structure-activity relationships revealed that introduction of a (hydroxy) acetyl group at N-1 of inactive 5-(3,4,5-trimethoxyphenyl) pyrazolines, results in a clear in vitro activating effect. Compound 31 (IC(50) = 5.16 mu M) showed inhibition of tubulin polymerization comparable to that of CA-4 (IC(50) = 4.92 mu M). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.037
• 作为产物：
  描述：

  没食子酸 在 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 1-(3’,4,’5’-trimethoxyphenyl)-3-[4-(N,N-dimethylaminophenyl)]-prop-2-enone
  参考文献：
  名称：

  基于没食子酸的查尔酮 Indl 2 通过抑制外排泵转运蛋白的协同抗菌活性

  摘要：

  作为从自然资源中新发现药物的一部分，本研究旨在探索查尔酮Indl-2与不同组抗生素联合使用的抗菌潜力。两种查尔酮对不同大肠杆菌培养物的抗生素 MIC 降低了八倍。这两种化合物中，即1-(3', 4,'5'-三甲氧基苯基)-3-(3-Indyl)-prop-2-enone ( 6, Indl-2 )，没食子酸的查尔酮衍生物( Indl-2 ) 与四环素 (TET) 协同作用效果更好，并且发现可以抑制外排转运蛋白，这一点通过 ATP 酶测定和对接研究证实的溴化乙锭外排是明显的。联合起来， Indl-2杀死MDREC−KG4细胞，TET的抗生素后效应（PAE）延长，并且TET的突变预防浓度（MPC）也降低。体内研究表明， Indl-2可降低 TNF-α 的浓度。在急性口服毒性研究中， Indl-2无毒且耐受性良好，剂量高达 2000 mg/kg。也许，该研究将报道没食子酸衍生的查耳酮作为协同剂通过抑制初级外排泵发挥作用。

  DOI：

  10.1002/cbdv.202301820

文献信息

• Evaluation and Discovery of Novel Synthetic Chalcone Derivatives as Anti-Inflammatory Agents
  作者：Jianzhang Wu、Jianling Li、Yuepiao Cai、Yong Pan、Faqing Ye、Yali Zhang、Yunjie Zhao、Shulin Yang、Xiaokun Li、Guang Liang

  DOI：10.1021/jm200946h

  日期：2011.12.8

  Major anti-inflammatory agents, steroids and cyclooxygenase, were proved to have serious side effects. Here, a series of chalcone derivatives were synthesized and screened for anti-inflammatory activities. QSAR study revealed that the presence of electron-withdrawing groups in B-ring and electron-donating groups in A-ring of chalcones was important for inhibition of LPS-induced IL-6 expression. Further

  事实证明，主要的抗炎药，类固醇和环氧合酶具有严重的副作用。在这里，合成了一系列查尔酮衍生物，并筛选了抗炎活性。QSAR研究表明，查耳酮的B环中有吸电子基团，而A环中有供电子基团对于抑制LPS诱导的IL-6表达很重要。此外，化合物22，23，26，40，和47抑制TNF-α和IL-6释放的剂量依赖的方式和降低LPS诱导的TNF-α，IL-1β，IL-6，IL-12，和COX-2 mRNA的产生。从机械上讲，化合物23和26干扰JNK /NF-κB信号传导并剂量依赖性地阻止ERK和p38激活。另外，23和26对LPS诱导的死亡显示出显着的保护作用，并且能够阻断巨噬细胞中高葡萄糖激活的细胞因子谱。总之，这些数据显示了一系列在炎性疾病中具有潜在治疗作用的抗炎查耳酮。
• Characterization of the Fluorescence Properties of 4-Dialkylaminochalcones and Investigation of the Cytotoxic Mechanism of Chalcones
  作者：Bo Zhou、Peixin Jiang、Junxuan Lu、Chengguo Xing

  DOI：10.1002/ardp.201500434

  日期：2016.7

  structure–activity relationship in their cellular cytotoxicity, leading to the identification of structurally similar cytotoxic and non‐cytotoxic fluorescent chalcones as chemical probes. Confocal microscopy results revealed the co‐localization of the cytotoxic probe C8 and tubulin in cells, supporting tubulin as the direct cellular target responsible for the cytotoxicity of chalcones.

  了解负责查耳酮的各种生物活动的机制，特别是直接的细胞靶点，是一个未解决的挑战。在这里，我们制备了一系列荧光查耳酮衍生物作为化学探针，用于其机理研究。通过系统的物理化学表征，我们探索了它们阐明查耳酮细胞毒性作用模式的潜力。发现查耳酮的荧光对结构和环境因素高度敏感。在结构上，B 环上的 4-二烷基氨基、A 环取代基的合适电子性质以及查耳酮核心结构的平面构象对于最佳荧光至关重要。影响荧光的环境因素包括溶剂极性、pH、以及查耳酮与蛋白质和洗涤剂的相互作用。发现 18 种查耳酮在 DMSO 中的荧光亮度大于 6000 M-1 cm-1。然而，水显着地淬灭了荧光，尽管它可以在 BSA 或去污剂的存在下部分恢复。正如预期的那样，这些荧光查耳酮在其细胞细胞毒性方面表现出明显的构效关系，从而导致鉴定出结构相似的细胞毒性和非细胞毒性荧光查耳酮作为化学探针。共聚焦显微镜结果揭示了细胞毒性探针 C8 和微管蛋白在
• Synthesis of novel pyrazoline derivatives and the evaluation of death mechanisms involved in their antileukemic activity
  作者：Natália Marceli Stefanes、Jéssica Toigo、Mariana Franzoni Maioral、Amanda Virtuoso Jacques、Louise Domeneghini Chiaradia-Delatorre、Daiane Mari Perondi、Amanda Abdalla Biasi Ribeiro、Álisson Bigolin、Iris Mattos Santos Pirath、Bruna Fischer Duarte、Ricardo José Nunes、Maria Cláudia Santos-Silva

  DOI：10.1016/j.bmc.2018.12.012

  日期：2019.1

  therefore, the search for new molecules with antitumor activity, specific and selective for neoplastic cells, became a great challenge for researchers in the oncology field. As pyrazolines stand out in the literature for their great variety of biological activities, the aim of this study was to synthesize and evaluate the antileukemic activity of five new pyrazoline derivatives. All pyrazolines showed

  恶性肿瘤是全球范围内主要的死亡原因之一，血液系统恶性肿瘤包括急性白血病（AL）是最相关的癌症类型之一。当前可用的化学疗法与高发病率和高死亡率相关，因此，寻找对肿瘤细胞具有特异性和选择性的，具有抗肿瘤活性的新分子，成为肿瘤学领域研究人员的巨大挑战。由于吡唑啉因其多种生物活性而在文献中脱颖而出，因此本研究的目的是合成和评估五种新的吡唑啉衍生物的抗白血病活性。所有吡唑啉均具有足够的理化性质，具有良好的口服生物利用度。选择了两种未公开和最有效的吡唑啉衍生物用于进一步的实验。与非肿瘤细胞相比，这些化合物对白血病细胞具有高度选择性，并且不会引起人红细胞的裂解。此外，选定的吡唑啉诱导细胞周期停滞在G0 / G1期，并降低了细胞增殖标志物KI67。通过形态分析，评估磷脂酰丝氨酸残基暴露和DNA片段化，证实了所选吡唑啉诱导的凋亡细胞死亡。几个因素表明发生内在和外在凋亡。它们是：FasR表达增加；Bax在Bc
• Synthesis of New <i>N</i><sup>1</sup>-Substituted-5-aryl-3-(3,4,5-trimethoxyphenyl)-2-pyrazoline Derivatives as Antitumor Agents Targeting the Colchicine Site on Tubulin
  作者：Salwa Elmeligie、Nadia Abdalla Khalil、Eman Mohamed Ahmed、Soha Hussein Emam、Sawsan Abo-Bakr Zaitone

  DOI：10.1248/bpb.b16-00277

  日期：——

  A series of pyrazoline derivatives 2a–e, 3a–e and 4a–e structurally related to combretastatin A4 (CA-4) were synthesized and characterized by spectroscopic means and elemental analyses. In these compounds, the cis double bond of CA-4 was replaced with the pyrazoline ring aiming to enhance the cytotoxic effects displayed by CA-4 and to prevent the cis/trans isomerization that is associated with inactivation of CA-4. The cytotoxic activity of all new compounds was investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by the most active compounds 3d, 4a and e was evaluated. The cytotoxicity of 4e was correlated with induction of apoptosis and caspase-3 activation in vitro thus indicating the apoptotic pathway of anticancer effect of these compounds. Furthermore, in vivo evaluation of the synthesized compounds was carried out against Ehrlich’s ascites carcinoma (EAC) solid tumor grown in mice. Compounds 2c, 3a and e showed significant reduction in tumor weight, and about 2–4 fold increase in caspase-3 expression.

  合成了一系列与康柏拉斯汀A4（CA-4）结构相关的吡唑啉衍生物2a–e、3a–e和4a–e，并通过光谱学方法和元素分析进行了表征。在这些化合物中，CA-4的顺式双键被吡唑啉环取代，旨在增强CA-4表现出的细胞毒性作用，并防止与CA-4失活相关的顺/反异构化。所有新化合物的细胞毒性活性在体外对MCF-7和HCT-116细胞系进行了研究。对最活跃化合物3d、4a和e的微管聚合抑制作用进行了评估。体外研究表明，化合物4e的细胞毒性与凋亡诱导和caspase-3活化相关，因此指示了这些化合物的抗癌效果的凋亡途径。此外，对合成化合物在小鼠中的埃赫利希腹水癌（EAC）实体肿瘤进行了体内评估。化合物2c、3a和e显示出肿瘤重量显著降低，以及caspase-3表达增加约2–4倍。
• 3‐Arylindanones and related compounds as antiproliferative agents against colorectal cancer
  作者：Ankita Srivastava、Kusumoori Ravi、Kaneez Fatima、Mayank Maheshwari、Raghib Ashraf、Mohammad Hasanain、Pankaj Yadav、Hina Iqbal、Yogesh Kumar、Suaib Luqman、Debabrata Chanda、Feroz Khan、Karuna Shanker、Jayanta Sarkar、Arvind Singh Negi

  DOI：10.1111/cbdd.13574

  日期：2019.9

  derivatives were synthesized as anticancer agents. Two of the analogues, that is 7 and 22, exhibited significant antiproliferative activity against several human cancer cell lines. Both the compounds possessed antimitotic activity and induced apoptosis in DLD1 colorectal adenocarcinoma cells through activation of caspase pathways. In cell cycle analysis, both the compounds induced predominantly G2/M phase arrest

  合成了多种亚苄基茚满酮及其衍生物作为抗癌剂。其中的两个类似物，即7和22，表现出对几种人类癌细胞系的显着抗增殖活性。这两种化合物都具有抗有丝分裂活性，并通过激活caspase途径在DLD1大肠腺癌细胞中诱导凋亡。在细胞周期分析中，这两种化合物在DLD1细胞中主要诱导G2 / M期停滞。分子对接研究表明，化合物7占据了β-微管蛋白的秋水仙碱结合口袋。两种化合物在啮齿动物的急性口服毒性方面都是安全的。两种化合物都被进一步优化以获得更好的功效。