ethyl 2-hydroxyl-4-(4-nitrophenyl)-4-oxo-2-butenoate

• 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: ethyl 2-hydroxyl-4-(4-nitrophenyl)-4-oxo-2-butenoate
• 英文别名: ethyl 2-hydroxy-4-(4-nitrophenyl)-4-oxo-2-butenoate
• 化学式: C₁₂H₁₁NO₆
• 分子量: 265.222
• InChiKey: JZQDDAPLTBLLJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  106.74
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-hydroxyl-4-(4-nitrophenyl)-4-oxo-2-butenoate 在 盐酸羟胺 、 水 、 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 5-(4-硝基苯基)异噁唑-3-羧酸
  参考文献：
  名称：

  Discovery of Membrane-Bound Pyrophosphatase Inhibitors Derived from an Isoxazole Fragment

  摘要：

  Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of small mPPase inhibitors with 6-10 mu M IC50 values in the Thermotoga maritima test system. Promisingly, the compounds retained activity against Plasmodium falciparum mPPase in membranes and inhibited parasite growth.

  DOI：

  10.1021/acsmedchemlett.9b00537
• 作为产物：
  描述：

  草酸二乙酯 、 对硝基苯乙酮 在 sodium ethanolate 作用下， 反应 24.0h， 以90.6%的产率得到ethyl 2-hydroxyl-4-(4-nitrophenyl)-4-oxo-2-butenoate
  参考文献：
  名称：

  Discovery of novel guanidinophenylpyrazole human acrosin inhibitors by molecular hybridization

  摘要：

  一种新型人类精子头蛋白酶抑制剂 F3 是通过苯基吡唑和胍基苯甲酸盐抑制剂的分子杂交合理设计的。

  DOI：

  10.1039/c4md00160e

文献信息

• Discovery of novel guanidinophenylpyrazole human acrosin inhibitors by molecular hybridization
  作者：Juntao Zhao、Nannan Sun、Yue Gao、Diya Lv、Yang Liu、Yan Jiang、Guoqiang Dong、Qianqian Chen、Wei Li、Youjun Zhou、Ju Zhu、Chunquan Sheng、Jiaguo Lv

  DOI：10.1039/c4md00160e

  日期：——

  Novel human acrosin inhibitor F3 was rationally designed by molecular hybridization of the phenylpyrazole and guanidinobenzoate inhibitors.

  一种新型人类精子头蛋白酶抑制剂 F3 是通过苯基吡唑和胍基苯甲酸盐抑制剂的分子杂交合理设计的。
• 异噁唑类新型顶体酶抑制剂及其制备方法
  申请人：中国人民解放军第二军医大学

  公开号：CN104119287B

  公开（公告）日：2016-04-20

  本发明涉及一类新型的顶体酶抑制剂、其制备方法及其在制备男性抗生育药物中的应用。具体的，本发明涉及一类如式Ⅰ所示的新型的顶体酶抑制剂，其中各取代基的定义如说明书中所述。本发明还涉及所述顶体酶抑制剂的制备方法及其在制备男性抗生育药物中的应用。
• 吡唑类顶体酶抑制剂及其制备方法
  申请人：中国人民解放军第二军医大学

  公开号：CN104119275B

  公开（公告）日：2016-06-22

  本发明涉及一类新型的顶体酶抑制剂、其制备方法及其在制备男性抗生育药物中的应用。具体的，本发明涉及一类如式Ⅰ所示的新型的顶体酶抑制剂，其中各取代基的定义如说明书中所述。本发明还涉及所述顶体酶抑制剂的制备方法及其在制备男性抗生育药物中的应用。
• “On water” synthesis of N-unsubstituted pyrazoles: semicarbazide hydrochloride as an alternative to hydrazine for preparation of pyrazole-3-carboxylate derivatives and 3,5-disubstituted pyrazoles
  作者：Violeta Marković、Milan D. Joksović

  DOI：10.1039/c4gc02028f

  日期：——

  A green, simple and highly efficient method for the synthesis of pyrazole-3-carboxylates and 3,5-disubstituted pyrazoles by cyclization of 4-aryl(hetaryl, alkyl)-2,4-diketoesters and 1,3-diketones with semicarbazide hydrochloride under “on water” conditions has been developed. This method also does not require toxic hydrazine and product purification, eliminating the use of toxic liquid chemicals.

  一种绿色，简单且高效的方法，通过用氨基脲盐酸盐将4-芳基（杂芳基，烷基）-2,4-二酮酸酯和1,3-二酮环化，合成吡唑-3-羧酸酯和3,5-二取代的吡唑在“水上”条件下已经开发出来。该方法也不需要毒性肼和产物纯化，从而消除了对有毒液体化学物质的使用。
• 3-Aroylmethylene-2,3,6,7-tetrahydro-1<i>H</i>-pyrazino[2,1-<i>a</i>]isoquinolin-4(11b<i>H</i>)-ones as Potent Nrf2/ARE Inducers in Human Cancer Cells and AOM-DSS Treated Mice
  作者：Mei-yang Xi、Jian-min Jia、Hao-peng Sun、Zhong-ying Sun、Jie-wei Jiang、Ya-jing Wang、Min-ye Zhang、Jun-feng Zhu、Li-li Xu、Zheng-yu Jiang、Xin Xue、Ming Ye、Xi Yang、Yuan Gao、Lei Tao、Xiao-ke Guo、Xiao-li Xu、Qing-long Guo、Xiao-jin Zhang、Rong Hu、Qi-dong You

  DOI：10.1021/jm400944k

  日期：2013.10.24

  Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house database of our laboratory. The potency of 1 was evaluated by the expression of NQO-1, HO-1, and nuclear translocation of Nrf2 in HCT116 cells. In vivo potency of 1 was studied using AOM-DSS models, showing that the development of colorectal adenomas was significantly inhibited. Administration with 1 lowered the expression of IL-6, IL-1 beta, and promoted Nrf2 nuclear translocation. These results indicated that 1 is a potent Nrf2/ARE activator, both in vitro and in vivo. Forty-one derivatives were synthesized for SAR study, and a more potent compound 17 was identified. To our knowledge, this is a potent ARE activator. Besides, its novel structure makes it promising for further optimization.