2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide | 662157-81-5

• 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: 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide
• 英文别名: 5-(2,4-Difluorophenyl)-2-hydroxy-benzohydrazide；5-(2,4-difluorophenyl)-2-hydroxybenzohydrazide
• CAS: 662157-81-5
• 化学式: C₁₃H₁₀F₂N₂O₂
• 分子量: 264.231
• InChiKey: ZROCOAXTQULQOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-(2',4'-difluoro-4-hydroxybiphenyl-3-carbonylhydrazono)-3-methyl-4-thiazolidinone
  参考文献：
  名称：

  Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide

  摘要：

  Two novel series of 4-thiazolidinone derivatives, namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4-thiazol idinone-3 -y1jam ides (5a-g) and 2-(2',4'-difluoro4-hydroxybipheiiyl-3-carbonylhydrazono)-3-alkyl/ary1-4-thiazolidinones (6ae) together with 5-(2',4'-difluoro4-hydroxybiphenyl-5-yi)-2-cyclohexylamino-1,3,4-oxadiazole (7a) have been synthesized as title compounds. 1-(2',4'-Difluoro-4-hydroxybiphenyl-3-carbonyl)4-alkyl/atylthiosemicarbazides (4a-g) were also obtained and used as intermediate to give the title compounds. All synthesized compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, antiviral and antimicrobial activities against various virus, bacteria and fungi strains. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.005
• 作为产物：
  描述：

  二氟尼柳 在 硫酸 、 一水合肼 作用下， 以 甲醇 为溶剂， 生成 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide
  参考文献：
  名称：

  作为环氧合酶抑制剂的二氟尼柳衍生物的合成、分子对接和抗癌活性

  摘要：

  环氧合酶在人体内的炎症通路中起着至关重要的作用。除了它们与炎症的关系之外，最近还发现了 COX-2 酶与癌症活性的额外关系。在某些癌症类型中，COX-2 酶的水平升高，表明该酶可能是癌症治疗的合适靶点。基于这些发现，我们合成了一些新的二氟尼柳缩氨基硫脲和 1,2,4-三唑，并针对雄激素非依赖性前列腺腺癌 (PC-3)、结肠癌 (HCT-116)、人类乳腺癌 (T47D)、乳腺癌 (MCF7) 和人胚胎肾 (HEK-293) 细胞系。具体而言，二氟尼柳和氨基硫脲官能团在预期效力增强的原始化合物的合成过程中结合。化合物 6、10、图15和16未显示对HEK293细胞系的细胞毒性作用。其中，化合物15和16显示出对乳腺癌细胞系T47D的抗癌活性，而作为氨基硫脲衍生物的化合物6和10显示出对PC-3细胞系的抗肿瘤活性，与文献一致。然而，对于带有测试的氨基硫脲衍生物的 HCT-116 癌细胞系没有观察到活性。只有化合物

  DOI：

  10.3390/molecules23081969

文献信息

• Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as Anti-HCV and Anticancer Agents
  作者：Sevil Aydın、Neerja Kaushik-Basu、Suna Özbaş-Turan、Jülide Akbuğa、Pınar Mega Tiber、Oya Orun、K. R. Gurukumar、Amartya Basu、Ş Güniz Küçükgüzel

  DOI：10.2174/15701808113109990069

  日期：2013.12.31

  1-Aroyl-3,5-dimethyl-1H-pyrazole derivatives (7-12) were synthesized from some hydrazides (1-6) with acetylacetone (2,4-pentanedione) by microwave irradiation. Their structures were elucidated by FT-IR and 1H-NMR spectral data and elemental analysis. Compound activities were evaluated against HCV NS5B and in cell based HCV reporters. Compound 8 was the most promising of this series in inhibiting intracellular NS5B activity and HCV RNA replication in reporter cells. The selected compounds 9, 10 and 12 by National Institue of Health were screened for their anticancer activity against 60 human tumor cell lines. Compound 9 (3-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-2',4'- difluorobiphenyl-4-ol) possessed significant activity against human immortalized myelogenous leukemia (K-562) exhibiting cell growth promotion 30.05%, with inhibition of 69.95% at 10-5M concentration. Compounds 3 and 9 were evaluated for cell viability and growth inhibition by K-562 cells of MTT assay, at different doses (10-6- 10-2M). Further, compound 9 exhibited anticancer activity against K-562 cells with IC50 value of 4 µM . Apoptosis levels of compound 9 were determined for three different concentrations (10-6, 10-5 and 10-3M) at two time points (24 and 48 h). Compound 9 induced apoptosis of K-562 cells, thus suggesting that compound 9 might be a potential chemopreventive agent for chronic myelogenous leukemia.

  1-芳酰基-3,5-二甲基-1H-吡唑衍生物（7-12）通过微波辐射从某些酰肼（1-6）与乙酰丙酮（2,4-戊二酮）合成。它们的结构通过FT-IR和1H-NMR光谱数据以及元素分析得到阐明。化合物活性针对HCV NS5B进行评估，并在基于细胞的HCV报告系统中进行测试。化合物8在这一系列中表现最为突出，抑制细胞内NS5B活性及HCV RNA在报告细胞中的复制。国家卫生研究院选定的化合物9、10和12，针对60种人类肿瘤细胞系进行了抗癌活性筛选。化合物9（3-[(3,5-二甲基-1H-吡唑-1-基)羰基]-2',4'-二氟联苯-4-醇）对人类永生化髓系白血病（K-562）表现出显著活性，细胞生长促进率为30.05%，在10-5M浓度下抑制率为69.95%。化合物3和9通过MTT法在不同剂量（10-6至10-2M）下评估了细胞生存能力和K-562细胞的生长抑制。进一步地，化合物9对K-562细胞表现出抗癌活性，IC50值为4μM。化合物9在三个不同浓度（10-6、10-5和10-3M）及两个时间点（24和48小时）下诱导凋亡水平。化合物9诱导K-562细胞凋亡，表明它可能成为慢性髓系白血病的潜在化学预防剂。
• Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors
  作者：Göknil Pelin Coşkun、Teodora Djikic、Sadık Kalaycı、Kemal Yelekçi、Fikrettin Şahin、Ş. Güniz Küçükgüzel

  DOI：10.2174/1570180815666180627130208

  日期：2019.3.8

  antibacterial activity in vitro against H. pylori. Results: All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2µg/ml MIC value. Conclusion: In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using

  背景：胃肠道溃疡治疗延长的主要因素是幽门螺杆菌感染，可能导致胃肠道癌。按照当今的标准，三联疗法是治疗的选择。但是，在细菌菌株中观察到的抗性会使情况变得更糟。因此，需要发现新的靶向抗菌疗法，以便成功地根除幽门螺杆菌感染。 方法：靶向治疗规则是确定导致细菌存活的相关大分子。因此，2-[（（2'，4'-二氟-4-羟基联苯-3-基）羰基] -N-（取代的）肼基碳硫代酰胺（3-13）和5-（2'，4'-二氟-4-合成了羟基联苯-3-基）-4-（取代）-2,4-二氢-3H-1,2,4-三唑-3-硫酮（14-17）并评估了其对幽门螺杆菌的体外抗菌活性。 结果：与标准药物（奥硝唑，甲硝唑，硝唑胺和克拉霉素）相比，所有测试化合物均显示出显着的抗菌活性。化合物4和13的活性为2μg/ ml MIC值。 结论：此外，我们还使用分子对接工具研究了化合物4和13与脲酶活性的结合方式和能量。
• Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents
  作者：Ş. Güniz Küçükgüzel、İlkay Küçükgüzel、Esra Tatar、Sevim Rollas、Fikrettin Şahin、Medine Güllüce、Erik De Clercq、Levent Kabasakal

  DOI：10.1016/j.ejmech.2006.12.038

  日期：2007.7

  4-oxadiazoles (6a-g) have been synthesized. Twenty-one of the newly synthesized compounds were tested against various bacteria, fungi, yeast species and virus. In addition, we have replaced the carboxylic acid group of diflunisal with heterocycles and the anti-inflammatory activity of heterocycles reported here. Compound (5d) showed activity against Escherichia coli A1 and Streptococcus pyogenes ATCC-176

  3个新颖的2'，4'-二氟-4-羟基联苯-3-羧酸衍生物系列，即4-取代的1,2,4,3-三唑啉-3-硫酮（4a-g）；已经合成了2-取代的1,3,4-噻二唑（5a-g）和2-取代的1,3,4-恶二唑（6a-g）。测试了二十一种新合成的化合物对各种细菌，真菌，酵母菌和病毒的抵抗力。此外，我们已用杂环取代了双氟尼醛的羧酸基团，并报道了杂环的抗炎活性。化合物（5d）以31.25μg/ mL的浓度显示出对大肠杆菌A1和化脓性链球菌ATCC-176的活性，而已发现用作标准药物的头孢吡肟对上述细菌的活性较低。化合物（4b）在浓度为31.25和15.25 microg / mL时对杂色曲霉和红毛癣菌表现出活性，而已发现用作标准品的两性霉素B对酵母和真菌的活性较低。在对Sindbis病毒的第2位具有甲基的1,3,4-噻二唑衍生物（5a）中，发现最高的抗病毒活性为9.6 microg / mL。化合物（4c）表现出最高的抗炎活性（73
• Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers
  作者：Sevil Şenkardeş、M. İhsan Han、Merve Gürboğa、Özlem Bingöl Özakpinar、Ş. Güniz Küçükgüzel

  DOI：10.1007/s00044-021-02837-z

  日期：2022.2

  4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50 = 17.8 μM and 21.2 μM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to

  本研究合成了28个含腙和磺酸根的杂化分子，除元素分析外，还通过FTIR、1 H-NMR、13 C-NMR光谱和LC-MS光谱对其进行了表征。评估了这些化合物对六种癌细胞系的抗增殖作用，即 A549（非小细胞肺癌）、MCF-7（乳腺癌）、HT-29（结直肠腺癌）、PC-3（雄激素非依赖性前列腺癌）腺癌）、Hep3B（肝细胞癌）和 HeLa（上皮样子宫颈癌）。在所有目标化合物中，化合物4g和4h对 MCF-7 细胞系表现出更有希望的作用（IC 50 = 17.8 μM 和 21.2 μM，分别）具有高选择性。进一步的机制研究表明，化合物4g和4h诱导的细胞凋亡是通过内在的凋亡途径介导的，通过最终激活 caspase-9 和 caspase-3 改变线粒体膜电位。结果令人鼓舞，值得进一步调查。
• [EN] HYDRAZONES AND THIAZOLIDINONES DERIVED FROM DIFLUNISAL<br/>[FR] HYDRAZONES ET THIAZOLIDINONES DÉRIVÉES DE DIFLUNISAL
  申请人：KUCUKGUZEL SUKRIYE GUNIZ

  公开号：WO2014137301A1

  公开（公告）日：2014-09-12

  It has been aimed in this invention to synthesize novel compounds having an original diflunisal hydrazide-hydrazone and 4-thiazolidone structures which may have the effect to inhibit DNA gyrase enzymes and which may be anticancer and HCV-NS5B polymerase obtained via diflunisal hydrazide produced by using Diflunisal which is a medical active substance which has a nonsteroidal anti-inflammatory effect () and which comprises a carboxylic acid structure.

  本发明的目的是合成具有原始二氟尼沙酰肼-肼酮和4-噻唑酮结构的新化合物，这些化合物可能具有抑制DNA酶旋转酶酶和可能具有抗癌和HCV-NS5B聚合酶的作用，通过使用具有非甾体抗炎作用的医用活性物质二氟尼沙酰肼生产的。该医用活性物质具有羧酸结构。