(Z)-4-[(3,4-dimethylphenyl)amino]-4-oxobut-2-enoic acid | 85843-38-5

• 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: (Z)-4-[(3,4-dimethylphenyl)amino]-4-oxobut-2-enoic acid
• 英文别名: (2z)-4-((3,4-Dimethylphenyl)amino)-4-oxobut-2-enoic acid；(Z)-4-(3,4-dimethylanilino)-4-oxobut-2-enoic acid
• CAS: 85843-38-5
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: BKCZXPVWUVICKC-WAYWQWQTSA-N

物化性质

• 熔点：
  173 °C
• 沸点：
  454.7±45.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  (Z)-4-[(3,4-dimethylphenyl)amino]-4-oxobut-2-enoic acid 在 sodium acetate 、 乙酸酐 作用下， 以80%的产率得到1-(3,4-二甲基苯基)-1H-吡咯-2,5-二酮
  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
• 作为产物：
  描述：

  马来酸酐 、 3,4-二甲基苯胺 以 氯仿 为溶剂， 生成 (Z)-4-[(3,4-dimethylphenyl)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

• [2+2]-Cycloaddition von Ketenen an �Maleinisoimide� und �berf�hrung der spiroverkn�pften ??-Laktame in Mucons�ure- und Tetrams�urederivate
  作者：Hans-Georg Capraro、Pierre Martin、Tammo Winkler

  DOI：10.1002/hlca.19830660132

  日期：1983.2.2

  [2+2]-Cycloaddition of ‘Maleic Isoimides’ with Ketenes and Reactions of Spiro-b̃-lactams to Muconic and Tetramic Acids

  [2 + 2]-顺丁烯二酮与马来酸的环加成反应及螺-β-内酰胺类化合物对粘康酸和四酸的反应
• MALEIC ACID DERIVATIVE, PRODUCTION METHOD FOR SAME, AND ANTI-CANCER COMPOSITION COMPRISING SAME
  申请人：Medicinal Bioconvergence Research Center

  公开号：US20160152607A1

  公开（公告）日：2016-06-02

  A maleic acid derivative represented by Chemical Formula 1 below or a pharmaceutically acceptable salt thereof: wherein, A is 5- to 7-membered phenyl having a substituent group, or heteroaryl or heterocycloalkyl containing at least one heteroatom selected from the group consisting of N, O, and S and having a substituent group, or 5- to 7-membered phenyl, heteroaryl, or heterocycloalkyl linked to C 1 -C 5 straight- or branched-chain alkyl, wherein the substituent group is unsubstituted, halogen, OH, OR 1 , nitro, nitrile, NH 2 , NHR 1 , NR 1 R 2 COOH, COOR 1 , CONH 2 , CONHR 1 , C 1 -C 5 straight- or branched-chain alkyl, phenyl, heteroaryl, or 5- to 7-membered heterocycloalkyl, where R 1 and R 2 each are C 1 -C 5 straight- or branched-chain alkyl, or phenyl or heteroaryl having a substituent group.

  下面化学式1所示的马来酸衍生物或其药学上可接受的盐：其中，A是带有取代基的5-至7-成员苯基，或含有来自N、O和S组成的群中至少一个杂原子的杂芳基或杂环烷基并带有取代基，或与C1-C5直链或支链烷基连接的5-至7-成员苯基、杂芳基或杂环烷基，其中取代基未取代、卤素、OH、OR1、硝基、腈、NH2、NHR1、NR1R2COOH、COOR1、CONH2、CONHR1、C1-C5直链或支链烷基、苯基、杂芳基或5-至7-成员杂环烷基，其中R1和R2各自是C1-C5直链或支链烷基，或带有取代基的苯基或杂芳基。
• NOVEL MALEIC ACID DERIVATIVE, PRODUCTION METHOD FOR SAME AND ANTI-CANCER COMPOSITION COMPRISING SAME
  申请人：Medicinal Bioconvergence Research Center

  公开号：EP3006428A1

  公开（公告）日：2016-04-13

  The present invention relates to a novel anticancer composition, and more specifically relates to a maleic acid derivative compound of Chemical Formula 1, to a production method for the compound, and to a pharmaceutical composition comprising the compound. The maleic acid derivative of the present invention suppresses the expression of AIMP2-DX2 and hence selectively suppresses the growth of cancer cell lines without acting on normal cells, and thus pharmaceutical compositions containing the maleic acid derivative of the present invention and pharmaceutically acceptable salts thereof as active ingredients can be used to prevent and treat cancer.

  本发明涉及一种新型抗癌组合物，更具体地说，涉及一种化学式1的马来酸衍生物化合物、该化合物的生产方法以及含有该化合物的药物组合物。本发明的马来酸衍生物可抑制 AIMP2-DX2 的表达，从而选择性地抑制癌细胞株的生长，而不作用于正常细胞，因此含有本发明的马来酸衍生物及其药学上可接受的盐类作为活性成分的药物组合物可用于预防和治疗癌症。
• Synthesis and biological evaluation of novel benzylidene-succinimide derivatives as noncytotoxic antiangiogenic inhibitors with anticolorectal cancer activity in vivo
  作者：Kaixiu Luo、Yafeng Bao、Feifei Liu、Chuanfan Xiao、Ke Li、Conghai Zhang、Rong Huang、Jun Lin、Jihong Zhang、Yi Jin

  DOI：10.1016/j.ejmech.2019.06.094

  日期：2019.10

  A novel series of benzylidene-succinimide derivatives were synthesized, characterized and evaluated for their cytotoxicities against HCT116, and SW480 cancer cells and NCM460 normal human cells. Their antiangiogenic capabilities were evaluated using a chick chorioallantoic membrane (CAM) assay. The compound, XCF-37b, was selected as the most potent antiangiogenic inhibitor with noncytotoxicity to evaluate the pharmacological effects on human umbilical vein endothelial cells (HUVECs) and cancer cells in vivo and in vitro. The results showed that XCF-37b inhibited HT29-cell colon tumor growth in vivo, without showing cytotoxicity against the five other cancer cell lines in vitro. Experiments confirmed that XCF-37b had obvious antiangiogenic activity by HUVEC migration and invasion and rat aortic ring angiogenesis ex vivo. Mechanism studies showed that XCF-37b inhibited the AKT/mTOR and VEGFR2 signaling pathways, as evidenced by decreased expressions of phosphor-AKT (p-AKT), p-mTOR, p-VEGFR2 (Tyr175), p-Src (Tyr416), p-FAK (Tyr925), and p-Erk1/2 (Thr202/Tyr204). Moreover, XCF-37b significantly decreased the protein expressions of matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1 alpha (HIF-1 alpha). XCF-37b generally regulated angiogenic inhibition through several regulatory pathways, without significantly interfering with colorectal cancer cell growth. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Syntheses of 4-(3,5-Bisphenylmethylene-4-oxo-piperidin-1-yl)-4-oxo-but-2<b><i>Z</i></b>-enoic Acid Arylamides as Candidate Cytotoxic Agents
  作者：Amitabh Jha、Jonathan R. Dimmock

  DOI：10.1081/scc-120017198

  日期：2003.1.5

  The title compounds were designed and synthesized as candidate cytotoxic agents. They were synthesized by reacting 3,5-bisphenylmethylene-piperidin-4-one with the appropriate 3-arylcarbamoylacrylic acids. These reactions follow an unusual mechanism and deviate from the previously reported reactions on similar substrates.