(E)-4-((4-methylphenyl)amino)-4-oxobut-2-enoic acid | 37904-23-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-((4-methylphenyl)amino)-4-oxobut-2-enoic acid
• 英文别名: (E)-oxo-4-((4-methylphenyl)amino)-4-oxobut-2-enoic acid；N-p-Tolylfumaramsaeure；4-[(4-Methylphenyl)amino]-4-oxobut-2-enoic acid；(E)-4-(4-methylanilino)-4-oxobut-2-enoic acid
• CAS: 37904-23-7
• 化学式: C₁₁H₁₁NO₃
• mdl: MFCD00174100
• 分子量: 205.213
• InChiKey: VLWFSWMZGGZHGD-VOTSOKGWSA-N

物化性质

• 沸点：
  446.0±45.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-dibenzylidenepiperidin-4-one 、 (E)-4-((4-methylphenyl)amino)-4-oxobut-2-enoic acid 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 17.5h， 以81%的产率得到(E)-4-[(3E,5E)-3,5-dibenzylidene-4-oxo-1-piperidyl]-4-oxo-N-(p-tolyl)but-2-enamide
  参考文献：
  名称：

  E,E,E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: A topographical study of some novel potent cytotoxins

  摘要：

  A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 mu M. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.065
• 作为产物：
  描述：

  反丁烯二酰氯 、 乙烷,三氯氟- 在 sodium hydroxide 、 盐酸 作用下， 生成 (E)-4-((4-methylphenyl)amino)-4-oxobut-2-enoic acid
  参考文献：
  名称：

  含有细胞毒性 1,4-dioxo-2-butenyl 药效团的芳胺衍生物

  摘要：

  已制备了若干系列含有 1,4-二氧-2-丁烯基部分的化合物作为候选细胞毒素，包括N-芳基马来酸甲酯、N-芳基富马酸甲酯和N-芳基马来酰亚胺。此外，合成了N-芳基异马来酰亚胺，它是N-芳基马来酰亚胺的结构异构体。这些化合物针对人 Molt 4/C8 和 CEM T 淋巴细胞以及鼠 L1210 细胞进行了评估。N-芳基富马酸甲酯显示出最高的细胞毒性效力，尤其是甲基N-(3,4-二氯苯基)富马酸盐对 L1210 细胞的作用是马法兰的六倍，在 Molt 4/C8 试验中与该药物等效。通过使用模型苄基硫醇对代表性化合物进行硫醇化来证明所研究化合物的亲电性。甲基ñ - （3,4-二氯苯基）fumaramate和甲基ñ - （4-氯苯基）马来酰胺酸抑制人Ñ -myristoyltransferase，可能的分子靶标，在高微摩尔范围。QSAR 和分子建模揭示了许多分子的不同结构特征与细胞毒性效力之间的一些

  DOI：

  10.1016/j.bmcl.2010.01.098

文献信息

• Facile esterification of carboxylic acids with organophosphorus reagents
  作者：V. Balasubramaniyan、V.G. Bhatia、S.B. Wagh

  DOI：10.1016/s0040-4020(01)88552-5

  日期：1983.1

  A mixture of alkyl phosphate esters (APE) obtained from P4O10 and alkanols taken in 1:6 mole ratio is an excellent esterification reagent for several classes of carboxylic acids. This new reagent offers several advantages compared to conventional reagents.

  由P 4 O 10获得的烷基磷酸酯（APE）和以1：6摩尔比获得的链烷醇的混合物是用于几类羧酸的优良酯化试剂。与常规试剂相比，这种新试剂具有多个优点。
• Design, synthesis and biological evaluation of novel spiro-quinazolinone derivatives as chitin synthase inhibitors and antifungal agents
  作者：Chuanbiao Du、Xinlong Yang、Yan Long、Xueqing Lang、Lige Liu、Yajie Xu、Hu Wu、Yiwen Chu、Xiaolei Hu、Junfeng Deng、Qinggang Ji

  DOI：10.1016/j.ejmech.2023.115388

  日期：2023.7

  quinazolinone and the inherent feature of spirocycle to design novel chitin synthase inhibitors that possess mode of action different from that of the currently used antifungal agents. Among them, the spiro[thiophen-quinazolin]-one derivatives containing α, β-unsaturated carbonyl fragments had shown inhibitory activities against chitin synthase and antifungal activities. The enzymatic experiments showed that

  基于喹唑啉酮的生物活性和螺环的固有特性，构建了一系列螺环喹唑啉酮支架，设计出与目前使用的抗真菌药物作用方式不同的新型几丁质合酶抑制剂。其中，含有α，β-不饱和羰基片段的螺[噻吩-喹唑啉]-酮衍生物显示出对几丁质合酶的抑制活性和抗真菌活性。酶促实验表明，在16个化合物中，化合物12d、12g、12j、12l和12m对几丁质合酶具有抑制作用，IC50值分别为 116.7 ± 19.6 μM、106.7 ± 14.2 μM、102.3 ± 9.6 μM、122.7 ± 22.2 μM 和 136.8 ± 12.4 μM，与多氧菌素 B (IC 50  = 93.5 ± 11.1 μM)相当。酶促动力学参数测定表明化合物12g是几丁质合酶的非竞争性抑制剂。抗真菌试验表明，化合物12d、12g、12j、12l和12m对体外测试的四种菌株表现出广谱抗真菌活性。其中，化合物12g和12j化合物 12d、12l
• Patel, M. V.; Balasubramaniyan, V., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. <B> 20, # 9, p. 804 - 805
  作者：Patel, M. V.、Balasubramaniyan, V.

  DOI：——

  日期：——
• Spectroscopic Investigation of Para-Methyl and Para-Methoxy Maleanilinic Acids in Comparison with Thermal Analyses and Theoretical Calculations and Evaluation of Cytotoxicity Against Carcinoma Cells
  作者：mohamed Zayed、Mohamed El-Desawy、AZZA Eladly

  DOI：10.21608/ejchem.2019.7353.1597

  日期：2019.3.7

  TWO NOVEL N-maleanilinic acid derivatives (I-II) namely (E)-oxo-4-((4-methyl phenyl) amino)-4-oxobut-2-enoic acid (p-MMA) and (E)-4-((4-methoxy phenyl) amino)-4oxobut-2-enoic acid (p-MOMA) were prepared by solvent free reaction between maleic anhydride, p-methyl and p-methoxy aniline derivatives in a good yield. These compounds were synthesized and investigated using elemental analyses, FT-IR and thermal analyses under argon atmosphere. The crystallographic structures of studied compounds were investigated by X-ray diffraction (XRD). The molecular structures of the titled compounds in the ground state were optimized by DFT/B3LYP and HF methods with 6-311G++ (d,p) basis set. Calculations were carried out by GAUSSIAN 09 suite of programs. Natural bond orbitals (NBO) analysis and frontier molecular orbitals were performed using NBO 3.1 program implemented in the Gaussian 09 package are presented at the same level of theory. These results were tabulated. This research aims chiefly to correlate between the structures of these investigated derivatives using experimental techniques in comparison with the theoretical molecular orbital (MO) calculated parameters. This correlation between experimental and theoretical calculations provided a good confirmation of the proposed structures of the newly prepared compounds. The derivatives were found to be highly effective against Hepatocellular carcinoma cells > Breast carcinoma cells > colon carcinoma cells. It was recognized, that cancer cells over expression promotes tumorigenic functions; were suppressed by p-MMA > p-MOMA inhibitors.
• RASTOGI R. P.; GIRI S.; SINGH H.; RASTOGI S., PROC. SYMP. CHEM. REACT. NON-AQUEOUS MEDIA AND MOLTEN SALTS, HYDERABAD, 1+
  作者：RASTOGI R. P.、 GIRI S.、 SINGH H.、 RASTOGI S.

  DOI：——

  日期：——