N-isonicotinoyl-N'-[3'-(4'''-nitrophenyl)-1'-phenyl-4'-pyrazolylmethylidene]hydrazine | 958965-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-isonicotinoyl-N'-[3'-(4'''-nitrophenyl)-1'-phenyl-4'-pyrazolylmethylidene]hydrazine
• 英文别名: N'-((3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)isonicotinohydrazide；N-[[3-(4-nitrophenyl)-1-phenylpyrazol-4-yl]methylideneamino]pyridine-4-carboxamide
• CAS: 958965-18-9
• 化学式: C₂₂H₁₆N₆O₃
• 分子量: 412.407
• InChiKey: KVTHRYYEAVTAKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-isonicotinoyl-N'-[3'-(4'''-nitrophenyl)-1'-phenyl-4'-pyrazolylmethylidene]hydrazine 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 3-(4-methoxyphenyl)-1-(2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)prop-2-en-1-one
  参考文献：
  名称：

  Synthesis, biological valuation, and QSAR studies of novel pyrazole bearing pyridyl oxadiazole analogues as potential antimicrobial agents

  摘要：

  A new series of 1-(2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-3-(aryl)prop-2-en-1-ones (5a-l) were synthesized by a simple and efficient synthetic protocol. The newly synthesized compounds were characterized by IR, H-1 NMR, C-13 NMR and Mass spectroscopy. The resulting structural diversity was screened for its antimicrobial activity the following bacterial and fungal strains: two Gram-positive bacteria [Staphylococcus aureus (MTCC-96), Streptococcus pyogenes (MTCC-442)], two Gram-negative bacteria [Escherichia coli (MTCC-443), Pseudomonas aeruginosa (MTCC-1688)] and three fungal species (C. albicans, A. niger and A. clavatus). Following this, in vitro cytotoxicity activity against HeLa cell lines was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. The observations derived from the diverse assays were utilized for building classification models based on a binary QSAR approach termed recursive partitioning (RP) analysis to probe the physic-chemical properties influencing the SAR for molecules. The decision tree derived from RP analysis could highlight structural characteristics that discriminate the actives from inactives which can serve as guide to design molecules with improved potency. In silico ADME predictions were performed to gauge their pharmacokinetic, safety and drug likeness profile.

  DOI：

  10.1007/s00044-016-1511-4
• 作为产物：
  描述：

  1-(4-nitro-phenyl)-ethanone-phenylhydrazone 在 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 N-isonicotinoyl-N'-[3'-(4'''-nitrophenyl)-1'-phenyl-4'-pyrazolylmethylidene]hydrazine
  参考文献：
  名称：

  DEVELOPMENT OF NEW PYRAZOLE HYBRIDS AS ANTITUBERCULAR AGENTS: SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY

  摘要：

  目标：使用分子杂交方法合成新的1,3-二苯基吡唑衍生物9(a-f)和10(a-f)，用于抗结核和细胞毒性研究。方法：合成化合物的结构通过1H-NMR、13C-NMR和质谱进行确认。通过微板Alamar蓝试验(MABA)评估化合物和标准药物对结核分枝杆菌的抗结核活性。细胞毒性活性通过Sulforhodamine B (SRB)试验进行评估。使用Schrodinger进行分子对接和体外ADME预测研究。结果：结果显示，化合物9c、9d、10c和10d表现出显著的抗结核潜力，MIC < 20 μM。细胞毒性研究显示，活性化合物(9d、10a和10d)对HeLa癌细胞系无毒性，选择性指数 > 10。进行分子对接研究以研究合成化合物与InhA酶的结合取向和亲和力。结论：研究发现，1,3-二苯基吡唑杂合物与已知的抗结核药物结合，可能成为潜在的抗结核药物的前导化合物。体外分子对接研究有助于识别它们与靶酶之间的相应分子间配体-蛋白相互作用。ADME预测研究显示，这些化合物的药代动力学参数处于可接受范围内。

  DOI：

  10.22159/ijpps.2017v9i11.20469

文献信息

• Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity
  作者：Sumit Bansal、Manju Bala、Sharad Kumar Suthar、Shivani Choudhary、Shoumyo Bhattacharya、Varun Bhardwaj、Sumit Singla、Alex Joseph

  DOI：10.1016/j.ejmech.2014.04.045

  日期：2014.6

  A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 μM showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.
• Synthesis of some pyrazolylaldehyde N-isonicotinoyl hydrazones and 2,5-disubstituted 1,3,4-oxadiazoles as DNA photocleaving agents
  作者：M. Kumar、V. Kumar、V. Beniwal

  DOI：10.1007/s00044-015-1340-x

  日期：2015.7

  In search of potential biologically active compounds, some novel 2,5-disubstituted 1,3,4-oxadiazole derivatives have been prepared conveniently via oxidation of newly synthesized pyrazolylaldehyde N-isonicotinoyl hydrazones by (diacetoxyiodo)benzene in dichloromethane under mild reaction conditions. Compounds were obtained in excellent yields, and their structures have been established on the basis of their FT-IR, H-1, C-13 NMR, and mass spectral data. The DNA photocleavage potential for all the synthesized compounds was evaluated using agarose gel electrophoresis. It has been observed that oxadiazole derivatives showed a significant level of DNA photocleavage activity when compared with their corresponding hydrazones, and some modifications in the basic structure may lead to construct some potential chemotherapeutic agents in future.
• DEVELOPMENT OF NEW PYRAZOLE HYBRIDS AS ANTITUBERCULAR AGENTS: SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY
  作者：Sameer I. Shaikh、Zahid Zaheer、Santosh N. Mokale、Deepak K. Lokwani

  DOI：10.22159/ijpps.2017v9i11.20469

  日期：——

  Objective: synthesis of new 1, 3-diphenyl pyrazole derivatives 9(a-f) and 10(a-f) using molecular hybridization approach for antitubercular and cytotoxic studies.Methods: The structures of synthesized compounds were confirmed by 1H-NMR, 13C-NMR and mass spectra’s. The antitubercular activity of compounds and standard drugs were assessed against Mycobacterium tuberculosis using microplate Alamar Blue assay (MABA).  The cytotoxic activities were performed by Sulforhodamine B (SRB) assay. The molecular docking and in silico ADME prediction were studied by using Schrodinger.Results: The results reveals that the compounds 9c, 9d, 10c and 10d exhibited substantial antitubercular potential with MIC < 20 μM. The cytotoxic studies revealed that the active compounds (9d, 10a, and 10d) are non-toxic to HeLa cancer cell lines with selectivity index >10. The molecular docking study was performed to study the binding orientation and affinity of synthesized compounds for InhA enzyme.Conclusion: The study explored that the 1, 3-diphenyl pyrazole hybrids coupled with well known antitubercular drugs could be a potential lead for antitubercular agents. In-silico molecular docking study helps to identify their corresponding intermolecular ligand-protein interactions with target enzyme. Also ADME prediction studies revealed that the compounds were in acceptable range to have pharmacokinetic parameters.

  目标：使用分子杂交方法合成新的1,3-二苯基吡唑衍生物9(a-f)和10(a-f)，用于抗结核和细胞毒性研究。方法：合成化合物的结构通过1H-NMR、13C-NMR和质谱进行确认。通过微板Alamar蓝试验(MABA)评估化合物和标准药物对结核分枝杆菌的抗结核活性。细胞毒性活性通过Sulforhodamine B (SRB)试验进行评估。使用Schrodinger进行分子对接和体外ADME预测研究。结果：结果显示，化合物9c、9d、10c和10d表现出显著的抗结核潜力，MIC < 20 μM。细胞毒性研究显示，活性化合物(9d、10a和10d)对HeLa癌细胞系无毒性，选择性指数 > 10。进行分子对接研究以研究合成化合物与InhA酶的结合取向和亲和力。结论：研究发现，1,3-二苯基吡唑杂合物与已知的抗结核药物结合，可能成为潜在的抗结核药物的前导化合物。体外分子对接研究有助于识别它们与靶酶之间的相应分子间配体-蛋白相互作用。ADME预测研究显示，这些化合物的药代动力学参数处于可接受范围内。
• Synthesis, biological valuation, and QSAR studies of novel pyrazole bearing pyridyl oxadiazole analogues as potential antimicrobial agents
  作者：N. C. Desai、G. M. Kotadiya、A. R. Trivedi、V. M. Khedkar、P. C. Jha

  DOI：10.1007/s00044-016-1511-4

  日期：2016.4

  A new series of 1-(2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-3-(aryl)prop-2-en-1-ones (5a-l) were synthesized by a simple and efficient synthetic protocol. The newly synthesized compounds were characterized by IR, H-1 NMR, C-13 NMR and Mass spectroscopy. The resulting structural diversity was screened for its antimicrobial activity the following bacterial and fungal strains: two Gram-positive bacteria [Staphylococcus aureus (MTCC-96), Streptococcus pyogenes (MTCC-442)], two Gram-negative bacteria [Escherichia coli (MTCC-443), Pseudomonas aeruginosa (MTCC-1688)] and three fungal species (C. albicans, A. niger and A. clavatus). Following this, in vitro cytotoxicity activity against HeLa cell lines was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. The observations derived from the diverse assays were utilized for building classification models based on a binary QSAR approach termed recursive partitioning (RP) analysis to probe the physic-chemical properties influencing the SAR for molecules. The decision tree derived from RP analysis could highlight structural characteristics that discriminate the actives from inactives which can serve as guide to design molecules with improved potency. In silico ADME predictions were performed to gauge their pharmacokinetic, safety and drug likeness profile.