3-(4-甲氧基苯基)-1-苯基-1H-吡唑-4-羧酸 | 372107-36-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(4-甲氧基苯基)-1-苯基-1H-吡唑-4-羧酸
• 英文名称: 3-(4-methoxyphenyl)-1-phenylpyrazole-4-carboxylic acid
• 英文别名: 3-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-4-carboxylic acid
• CAS: 372107-36-3
• 化学式: C₁₇H₁₄N₂O₃
• mdl: MFCD02227818
• 分子量: 294.31
• InChiKey: QOTMSXYEJBWVMB-UHFFFAOYSA-N

物化性质

• 沸点：
  481.5±35.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.058
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  3-(4-甲氧基苯基)-1-苯基-1H-吡唑-4-羧酸 在 氯化亚砜 作用下， 反应 3.0h， 生成 3-(4-methoxyphenyl)-1-phenyl-4-pyrazolecarbonyl chloride
  参考文献：
  名称：

  通过抑制MEK，发现N-（苄氧基）-1,3-二苯基-1H-吡唑-4-羧酰胺衍生物作为潜在的抗增殖剂。

  摘要：

  丝裂原活化蛋白激酶（MAPK）信号转导途径已被证明在肿瘤发生和癌症发展中起重要作用。已经证明MEK抑制剂对于阻断MAPK途径活化具有显着的临床益处，并且可能在BRAF抑制剂抵抗时阻断MAPK途径的再活化。设计并合成了二十种N-（苄氧基）-1,3-二苯基-1H-吡唑-4-羧酰胺衍生物作为MEK抑制剂，并对其生物学活性进行了评估。在这些化合物中，化合物7b表现出最强的抑制活性，对MEK1的IC50为91nM，对A549细胞的GI50为0.26μM。进行了SAR分析和对接模拟，以提供可用于进一步结构优化的关键药效​​团线索。

  DOI：

  10.1016/j.bmc.2016.08.002
• 作为产物：
  描述：

  3-(4-甲氧基苯基)-1-苯基-1H-吡唑-4-甲醛 在 potassium permanganate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 0.75h， 生成 3-(4-甲氧基苯基)-1-苯基-1H-吡唑-4-羧酸
  参考文献：
  名称：

  新型芳基取代吡唑作为细胞色素 P450 CYP121A1 的小分子抑制剂：合成和抗分枝杆菌评估

  摘要：

  描述了三个系列的联芳基吡唑咪唑和三唑，它们在联芳基吡唑和咪唑/三唑基团之间的接头不同。具有短-CH 2 - 接头的咪唑和三唑系列显示出有希望的抗分枝杆菌活性，咪唑-CH 2 - 系列 ( 7 ) 显示出低 MIC 值 (6.25-25 μg/mL)，这也受到亲脂性的影响。将接头延伸至-C(O)NH(CH 2 ) 2 - 导致抗分枝杆菌活性丧失。化合物与 CYP121A1 的结合亲和力通过紫外-可见光滴定法测定，对于最紧密结合的化合物7e ， K D值分别为 2.63、35.6 和 290 μM、8b和13d来自它们各自的系列。CYP121A1 抑制剂的结合亲和力测定和对接研究表明 II 型通过间质水分子间接结合，具有关键结合残基 Thr77、Val78、Val82、Val83、Met86、Ser237、Gln385 和 Arg386，与用氟康唑观察到的结合相互作用相当和天然底物二环酪氨酸。

  DOI：

  10.1021/acs.jmedchem.7b01562

文献信息

• Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation
  作者：Ismail M. Taban、Hosam E. A. E. Elshihawy、Beyza Torun、Benedetta Zucchini、Clare J. Williamson、Dania Altuwairigi、Adeline S. T. Ngu、Kirsty J. McLean、Colin W. Levy、Sakshi Sood、Leonardo B. Marino、Andrew W. Munro、Luiz Pedro S. de Carvalho、Claire Simons

  DOI：10.1021/acs.jmedchem.7b01562

  日期：2017.12.28

  KD values of 2.63, 35.6, and 290 μM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions

  描述了三个系列的联芳基吡唑咪唑和三唑，它们在联芳基吡唑和咪唑/三唑基团之间的接头不同。具有短-CH 2 - 接头的咪唑和三唑系列显示出有希望的抗分枝杆菌活性，咪唑-CH 2 - 系列 ( 7 ) 显示出低 MIC 值 (6.25-25 μg/mL)，这也受到亲脂性的影响。将接头延伸至-C(O)NH(CH 2 ) 2 - 导致抗分枝杆菌活性丧失。化合物与 CYP121A1 的结合亲和力通过紫外-可见光滴定法测定，对于最紧密结合的化合物7e ， K D值分别为 2.63、35.6 和 290 μM、8b和13d来自它们各自的系列。CYP121A1 抑制剂的结合亲和力测定和对接研究表明 II 型通过间质水分子间接结合，具有关键结合残基 Thr77、Val78、Val82、Val83、Met86、Ser237、Gln385 和 Arg386，与用氟康唑观察到的结合相互作用相当和天然底物二环酪氨酸。
• Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)
  作者：Bing Zhao、Qianqian Liang、Hongmei Ren、Xinhui Zhang、Yang Wu、Kun Zhang、Li-Ying Ma、Yi-Chao Zheng、Hong-Min Liu

  DOI：10.1016/j.ejmech.2020.112161

  日期：2020.4

  KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent

  KDM5B（也称为PLU-1和JARID1B）是2-氧戊二酸和Fe 2+依赖性加氧酶，可作为组蛋白H3K4脱甲基酶，是抑制肿瘤抑制因子（作为药物靶标）表达的关键参与者。在这里，我们介绍了通过基于结构的虚拟筛选和生化筛选发现吡唑衍生物化合物5的效果，针对KDM5B的IC 50为9.320μM，随后对其进行了优化以得到1-（4-甲氧基苯基）-N-（2-甲基- 2-吗啉代丙基）-3-苯基-1H-吡唑-4-羧酰胺（27 ab），一种有效的KDM5B抑制剂，IC 50为0.0244μM 。在MKN45细胞中，化合物27 ab可以结合和稳定KDM5B并诱导H3K4me2 / 3（真正的KDM5B底物）积累，同时保持H3K4me1，H3K9me2 / 3和H3K27me2的含量不变。进一步的生物学研究还表明，化合物27 ab是一种有效的细胞活性KDM5B抑制剂，可以抑制MKN45细胞增殖，伤口愈合和迁移
• Synthesis of Novel 6-(1H-pyrazol-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles as Potential Antimicrobial Agents
  作者：Rashmi Pundeer、Pooja Ranjan、Richa Prakash、Radhika Joshi

  DOI：10.2174/1570178614666170907121125

  日期：2018.1.10

  Saccharomyces cervisiae. Results: A new series of 3-alkyl-6-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazoles has been synthesized by the reaction mentioned above. One specific compound, 6-(3-(4- fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-3-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole displayed an excellent antifungal activity against Candida albicans with a MIC value of 8 µg/ml

  背景：三唑并噻二唑是具有重大合成和药理意义的分子。它们与显着的抗菌，抗真菌，抗菌，抗蠕虫和抗炎活性有关。 方法：在磷酰氯存在下，将5-烷基-4-氨基-3-巯基-4H-1,2,4-三唑与3-芳基-1-苯基吡唑-4-羧酸缩合。体外测试所得产物对枯草芽孢杆菌（革兰氏阳性），金黄色葡萄球菌（革兰氏阳性），大肠杆菌（革兰氏阴性）和铜绿假单胞菌（革兰氏阴性）的抗菌潜力，以及对白色念珠菌和啤酒酵母的抗真菌性能。 结果：一系列新的3-烷基-6-（3-芳基-1-苯基-1H-吡唑-4-基）-[1,2,4]三唑[3,4-b] [1,3， [4]噻二唑通过上述反应合成。一种特定的化合物，6-（3-（4-氟苯基）-1-苯基-1H-吡唑-4-基）-3-甲基-[1,2,4]三唑[3,4-b] [1， 3,4]噻二唑对白色念珠菌显示出优异的抗真菌活性，MIC值为8 µg / ml，实际上甚至比标准药物两性霉素B（MIC 10
• Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors
  作者：V. Ganga Reddy、T. Srinivasa Reddy、V. Lakshma Nayak、Budaganaboyina Prasad、Adiyala Praveen Reddy、A. Ravikumar、Shaik Taj、Ahmed Kamal

  DOI：10.1016/j.ejmech.2016.06.011

  日期：2016.10

  A series of new (N4(1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-Pyrazole-4-carboxamide derivatives (8-35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI(50) values ranging from 0.13 to 0.7 mu M, compared with the positive control nocodazole (0.81-0.95 mu M). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7 cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhoda mine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model
  作者：Velma Ganga Reddy、T. Srinivasa Reddy、Chetna Jadala、M. Soumya Reddy、Faria Sultana、Ravikumar Akunuri、Suresh K. Bhargava、Donald Wlodkowic、P. Srihari、Ahmed Kamal

  DOI：10.1016/j.ejmech.2019.111609

  日期：2019.11

  A series of new pyrazolo-benzothiazole hybrids (7-26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17-6.77 mu M, even better than reference drug axitinib (4.88-21.7 mu M). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery. (C) 2019 Published by Elsevier Masson SAS.