ethyl-2-[2-(3-chloro-4-fluorophenyl)hydrazinylidene]-3-oxobutanoate | 753500-79-7

• 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: ethyl-2-[2-(3-chloro-4-fluorophenyl)hydrazinylidene]-3-oxobutanoate
• 英文别名: ethyl 2-(3-chloro-4-fluorophenyl)hydrazono-3-oxobutyrate；ethyl 2-[(3-chloro-4-fluorophenyl)hydrazinylidene]-3-oxobutanoate
• CAS: 753500-79-7
• 化学式: C₁₂H₁₂ClFN₂O₃
• 分子量: 286.69
• InChiKey: DYUCWCXNIIXGCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  0.25
• 拓扑面积：
  67.76
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl-2-[2-(3-chloro-4-fluorophenyl)hydrazinylidene]-3-oxobutanoate 在 盐酸 、 aluminum (III) chloride 作用下， 以 1,4-二氧六环 、 水 、 氯苯 为溶剂， 反应 16.0h， 生成 (7-Chloro-8-fluoro-3-methylpyrazolo[4,3-c]cinnolin-1-yl)-(4-methoxyphenyl)methanone
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents

  摘要：

  A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 41 showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory antibacterial agent in the present study. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.045
• 作为产物：
  描述：

  3-氯-4-氟苯胺 、 乙酰乙酸乙酯 在 盐酸 、 sodium nitrite 、 ammonium acetate 作用下， 以 水 、 乙醇 为溶剂， 反应 0.58h， 生成 ethyl-2-[2-(3-chloro-4-fluorophenyl)hydrazinylidene]-3-oxobutanoate
  参考文献：
  名称：

  新型N-甲基吡啶甲酰胺和硫代嘧啶衍生物作为选择性c-Met激酶抑制剂的合成及生物评价研究。

  摘要：

  设计并合成了带有哒嗪酮的四个系列的N-甲基吡啶甲基酰胺部分和噻吩并嘧啶部分，并评估了其对三种癌细胞系（A549，HepG2和MCF-7）的IC 50值，并进一步评估了一些所选化合物对c-的活性Met，Flt-3，VEGFR-2，c-Kit和EGFR激酶。三种化合物（35，39和43）比阳性对照Foretinib表现出更多的活性对A549，HepG2和MCF-7细胞系。最有前途的化合物43表现出对A549，HepG2和MCF-7的优异活性，其IC 50为500.58±0.15 µM，0.47±0.06 µM和0.74±0.12 µM的活性分别比福瑞替尼高3.73–5.39倍。基于酶的实验表明，有43种酶选择性抑制c-Met，IC 50值为16 nM，与Foretinib（14 nM）具有相同的活性，并且比化合物5（90 nM）更好。此外，还进行了AO和Annexin V / PI染色和对接研究。

  DOI：

  10.1016/j.bmc.2017.11.039

文献信息

• Synthesis and biological evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives
  作者：P. Horrocks、M. R. Pickard、H. H. Parekh、S. P. Patel、Ravindra B. Pathak

  DOI：10.1039/c3ob27290g

  日期：——

  3-(4-Chlorophenyl)-4-substituted pyrazole derivatives were synthesised and tested for their in vitro antifungal activity. Some compounds showed very good antifungal activity against four pathogenic strains of fungi. The same compounds exhibited an interesting activity against the tested strain of Mycobacterium tuberculosis H37Rv. The results suggest that 1,3,4-oxadiazoles and 5-pyrazolinones bearing

  合成了3-（4-氯苯基）-4-取代的吡唑衍生物，并测试了它们的体外抗真菌活性。一些化合物对四种病原性真菌显示出非常好的抗真菌活性。相同的化合物对测试的结核分枝杆菌H37Rv菌株表现出令人感兴趣的活性。结果表明，带有核心吡唑支架的1,3,4-恶二唑和5-吡唑啉酮可能是有前途的抗真菌和抗结核药。
• Type II diabetes-related enzyme inhibition and molecular modeling study of a novel series of pyrazolone derivatives
  作者：Shobhitha Shetty、Balakrishna Kalluraya、Nithinchandra、S. K. Peethambar、Sandeep B. Telkar

  DOI：10.1007/s00044-013-0846-3

  日期：2014.6

  Inhibitors of alpha-amylase are targets for the development of novel drugs for the treatment of diabetes and obesity. Alpha amylase is an enzyme which increases the bio availability of glucose in the blood. Hence, the inhibition effects of alpha amylase of 2-[1-(4-isobutylphenyl)ethyl]-5-methyl-4-[2-(aryl-substituted)hydrazinylidene]-2,4-dihydro-3H-pyrazol-3-one (4a-l) were investigated, among them compounds 4d, 4f, 4a, and 4g have displayed good inhibitory activity. The compounds with significant results were further evaluated for their molecular modeling study using in silico method. The new series of compounds were synthesized by solvent-free microwave irradiation method and were characterized by spectral and analytical data.
• Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinase inhibitors
  作者：Qidong Tang、Linxiao Wang、Yongli Duan、Wenhui Wang、Shunmin Huang、Jia Zhi、Shuang Jia、Wufu Zhu、Ping Wang、Rong Luo、Pengwu Zheng

  DOI：10.1016/j.ejmech.2017.03.045

  日期：2017.6

  A series of 7-azaindole derivatives bearing the dihydropyridazine scaffold were synthesized and evaluated for their c-Met kinase inhibitory, and antiproliferative activity against 4 cancer cell lines (HT29, A549, H460, U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency. Compared to foretinib, the most promising analog 34 (c-Met IC50: 1.06 nM, a multitarget tyrosine kinase inhibitor) showed a 6.4-, 7.8-, and 3.2-fold increase in activity against HT29, A549, and H460 cell lines, respectively. Structure activity relationship studies indicated that mono-EWGs (such as R-2 = F) at 4-position of moiety D was a key factor in improving the antitumor activity. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Jois, H.S. Vidyashree; Kalluraya, Balakrishna; Babu, Indian Journal of Heterocyclic Chemistry, 2015, vol. 25, # 1, p. 7 - 10
  作者：Jois, H.S. Vidyashree、Kalluraya, Balakrishna、Babu、Bhagya、Chandrashekar

  DOI：——

  日期：——
• Synthesis and bioevaluation study of novel N -methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors
  作者：Linxiao Wang、Shan Xu、Xiuying Chen、Xiaobo Liu、Yongli Duan、Dejia Kong、Dandan Zhao、Pengwu Zheng、Qidong Tang、Wufu Zhu

  DOI：10.1016/j.bmc.2017.11.039

  日期：2018.1

  Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Three compounds (35, 39 and 43) showed more active than positive control

  设计并合成了带有哒嗪酮的四个系列的N-甲基吡啶甲基酰胺部分和噻吩并嘧啶部分，并评估了其对三种癌细胞系（A549，HepG2和MCF-7）的IC 50值，并进一步评估了一些所选化合物对c-的活性Met，Flt-3，VEGFR-2，c-Kit和EGFR激酶。三种化合物（35，39和43）比阳性对照Foretinib表现出更多的活性对A549，HepG2和MCF-7细胞系。最有前途的化合物43表现出对A549，HepG2和MCF-7的优异活性，其IC 50为500.58±0.15 µM，0.47±0.06 µM和0.74±0.12 µM的活性分别比福瑞替尼高3.73–5.39倍。基于酶的实验表明，有43种酶选择性抑制c-Met，IC 50值为16 nM，与Foretinib（14 nM）具有相同的活性，并且比化合物5（90 nM）更好。此外，还进行了AO和Annexin V / PI染色和对接研究。