N'-[3'-(4'''-bromophenyl)-1'-phenyl-4'-pyrazolylmethylidene]-N-isonicotinoylhydrazine | 351471-51-7

• 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'-[3'-(4'''-bromophenyl)-1'-phenyl-4'-pyrazolylmethylidene]-N-isonicotinoylhydrazine
• 英文别名: N-[[3-(4-bromophenyl)-1-phenylpyrazol-4-yl]methylideneamino]pyridine-4-carboxamide
• CAS: 351471-51-7
• 化学式: C₂₂H₁₆BrN₅O
• 分子量: 446.306
• InChiKey: SPTASNADAUEZQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 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：
  72.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-[3'-(4'''-bromophenyl)-1'-phenyl-4'-pyrazolylmethylidene]-N-isonicotinoylhydrazine 在 碘苯二乙酸 作用下， 以 二氯甲烷 为溶剂， 以84%的产率得到4-(5-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)pyridine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.04.045
• 作为产物：
  描述：

  4-溴苯乙酮苯腙 在 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 N'-[3'-(4'''-bromophenyl)-1'-phenyl-4'-pyrazolylmethylidene]-N-isonicotinoylhydrazine
  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

• 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.
• 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.
• 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。