(Z)-4-(4-methoxybenzylidene)-2-p-tolyloxazol-5(4H)-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-4-(4-methoxybenzylidene)-2-p-tolyloxazol-5(4H)-one
• 英文别名: (4Z)-4-[(4-methoxyphenyl)methylidene]-2-(4-methylphenyl)-1,3-oxazol-5(4H)-one；4-(4-Methoxy-benzylidene)-2-p-tolyl-4H-oxazol-5-one；(4Z)-4-[(4-methoxyphenyl)methylidene]-2-(4-methylphenyl)-1,3-oxazol-5-one
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: ZWBVMAMDCKGKAA-WJDWOHSUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-4-(4-methoxybenzylidene)-2-p-tolyloxazol-5(4H)-one 在 ammonium hydroxide 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以15%的产率得到(4Z)-4-[(4-methoxyphenyl)methylidene]-2-(4-methylphenyl)-1H-imidazol-5-one
  参考文献：
  名称：

  Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

  摘要：

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.054
• 作为产物：
  描述：

  对甲基苯甲酰氯 在 potassium acetate 、 溶剂黄146 、 potassium hydroxide 作用下， 以 水 为溶剂， 生成 (Z)-4-(4-methoxybenzylidene)-2-p-tolyloxazol-5(4H)-one
  参考文献：
  名称：

  5-芳基恶唑酮的新型二螺衍生物的合成和细胞毒性，p53-MDM2蛋白-蛋白相互作用的潜在抑制剂

  摘要：

  在其结构中结合了吲哚酮和恶唑酮片段的新型二螺吲哚酮的区域选择性合成包括偶氮甲碱叶立德的 1,3-偶极环加成，由靛红和肌氨酸原位生成，在 2-芳基-5-芳基亚甲基取代的 1,3 -恶唑-5(4H)-酮。当邻位和对位卤素原子存在于起始恶唑酮的芳族取代基中时，会形成含有大量恶唑啉开环产物及其二螺衍生物的复杂混合物。通过 MTT 在 LNCaP、PC3、HCT116、MCF7、A549、HEK 和 VA13 细胞系上测试化合物的细胞毒性。具有最佳细胞毒性的化合物对表达 p53 的 LNCaP 细胞的 IC50 = 1.08±0.96 μM 和对不表达 p53 蛋白的 PC3 细胞的活性较低（IC50 = 3.21±1.45 μM），然而，

  DOI：

  10.1007/s11172-018-2111-x

文献信息

• Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4H)-ones and N-methyl-3,5-dihydro-4H-imidazol-4-ones as combretastatin A-4 analogs
  作者：E. S. Barskaia、A. A. Beloglazkina、B. Wobith、N. A. Zefirov、A. G. Majouga、E. K. Beloglazkina、N. V. Zyk、S. A. Kuznetsov、O. N. Zefirova

  DOI：10.1007/s11172-015-1041-0

  日期：2015.7

  A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC50 = 6±0.8 μmol L−1).

  合成了一系列2-芳基-5-芳基甲烯基-1,3-噁唑-5(4H)-酮和2-芳基-5-芳基甲烯基-N-甲基-3,5-四氢-4H-咪唑-4-酮，作为抗肿瘤活性化合物康柏树氨酸A-4的结构类似物。研究发现，（5Z）-5-[(4-甲氧基苯基)甲烯基]-3-甲基-2-(4-甲基苯基)-3,5-四氢-4H-咪唑-4-酮对人类A549肺癌细胞系表现出最高的细胞毒性（EC50 = 6±0.8 μmol L−1）。
• Catalytic aza-Wittig Reaction of Acid Anhydride for the Synthesis of 4<i>H</i>-Benzo[<i>d</i>][1,3]oxazin-4-ones and 4-Benzylidene-2-aryloxazol-5(4<i>H</i>)-ones
  作者：Long Wang、Yi-Bi Xie、Nian-Yu Huang、Jia-Ying Yan、Wei-Min Hu、Ming-Guo Liu、Ming-Wu Ding

  DOI：10.1021/acscatal.6b00165

  日期：2016.6.3

  copper-catalyzed reduction of phosphine oxide was used and found effective for this transformation. Additionally, the one-pot catalytic aza-Wittig reaction of carboxylic acids was achieved. Furthermore, NMR experiments and Hammett plot recorded the process of catalytic aza-Wittig reaction of anhydride, which provides direct proof that the copper-catalyzed reduction of waste phosphine oxide is the key step

  与醛，酮，酰胺和酯的aza-Wittig反应相比，酸酐的aza-Wittig反应总是被忽略，这应该是Wittig反应的重要组成部分。在这里，酸酐的aza-Wittig反应和酸酐的aza-Wittig催化反应均以高收率开发，这为合成4 H-苯并[ d ] [1,3]恶嗪-4-酮和4-亚苄基-2-芳基恶唑-5（4 H）-那些。使用了铜催化的氧化膦还原的策略，发现该策略对这种转化有效。另外，实现了羧酸的一锅催化的氮杂-维蒂希反应。此外，NMR实验和Hammett曲线记录了酸酐的催化氮杂-维蒂希反应过程，这直接证明了铜催化的废氧化膦的还原是该转化过程中的关键步骤。
• A domino approach for the synthesis of naphtho[2,1-b]furan-2(1H)-ones from azlactones
  作者：Elmira Salami-Ranjbaran、Ahmad R. Khosropour、Iraj Mohammadpoor-Baltork

  DOI：10.1016/j.tet.2014.05.067

  日期：2014.12

  A domino approach to naphtho[2,1-b]furan-2(1H)-one derivatives from (Z)-4-arylidene-2-phenyl-5(4)-oxazolones (azlactones) and 2-naphthols catalyzed by p-TSA with reasonably moderate to high yields, has been developed. This protocol illustrates attractive features including a unique and convenient process. (C) 2014 Published by Elsevier Ltd.
• Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy
  作者：Andreas P. Lill、Carmen B. Rödl、Dieter Steinhilber、Holger Stark、Bettina Hofmann

  DOI：10.1016/j.ejmech.2014.10.054

  日期：2015.1

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and cytotoxicity of novel dispiro derivatives of 5-arylidenoxazolones, potential inhibitors of p53—MDM2 protein-protein interaction
  作者：A. А. Beloglazkina、D. А. Skvortsov、V. A. Tafeenko、А. G. Majouga、N. V. Zyk、Е. К. Beloglazkina

  DOI：10.1007/s11172-018-2111-x

  日期：2018.3

  Regioselective synthesis of new dispiro indolinones combining both an indolinone and an oxazolone fragment in their structure comprised the 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from isatin and sarcosine, at 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4H)-ones. When ortho and para halogen atoms were present in the aromatic substituents of the starting oxazolones, complex

  在其结构中结合了吲哚酮和恶唑酮片段的新型二螺吲哚酮的区域选择性合成包括偶氮甲碱叶立德的 1,3-偶极环加成，由靛红和肌氨酸原位生成，在 2-芳基-5-芳基亚甲基取代的 1,3 -恶唑-5(4H)-酮。当邻位和对位卤素原子存在于起始恶唑酮的芳族取代基中时，会形成含有大量恶唑啉开环产物及其二螺衍生物的复杂混合物。通过 MTT 在 LNCaP、PC3、HCT116、MCF7、A549、HEK 和 VA13 细胞系上测试化合物的细胞毒性。具有最佳细胞毒性的化合物对表达 p53 的 LNCaP 细胞的 IC50 = 1.08±0.96 μM 和对不表达 p53 蛋白的 PC3 细胞的活性较低（IC50 = 3.21±1.45 μM），然而，