N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide

• 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: N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide
• 英文别名: N-[(E)-(4-phenoxyphenyl)methyleneamino]pyridine-4-carboxamide；N-[(E)-(4-phenoxyphenyl)methylideneamino]pyridine-4-carboxamide
• 化学式: C₁₉H₁₅N₃O₂
• 分子量: 317.347
• InChiKey: CCEYAAAISXFPAP-KGENOOAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide 在 盐酸 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 生成 N’-(4-phenoxybenzyl)isonicotinohydrazide
  参考文献：
  名称：

  异烟肼衍生物作为抗耐药结核病潜在药物的体外评价

  摘要：

  耐多药结核病的高发加剧了到2030年结束这一流行病的挑战。2020年因结核病死亡的人数比2019年增加，新发现的耐多药结核病病例稳定接近3% . 这种背景激发了对新的和更有效的抗结核化合物的研究，最终导致了面向 QSAR 的设计和合成一系列对抗结核有活性的异烟肼衍生物。结核分枝杆菌. 由此，本工作研究了一些有前景的异烟酰腙和异烟酰肼。评估化学衍生化是否产生具有良好性能的化合物体外测定，确定了它们对人肝HepG2细胞的细胞毒性，并彻底研究了它们结合人血清白蛋白的能力。对于本研究中提出的两种新衍生物，我们还确定了它们对野生型和异烟肼抗性菌株的亲脂性和活性。结核分枝杆菌携带最普遍的突变卡特格基因，S315T。所有化合物的细胞毒性都低于临床使用的许多药物，72 小时攻击后的 IC 50值始终高于 25 µM。此外，所研究的所有异烟肼衍生物与人血清白蛋白的结合比异烟肼本身更强，解离常数分别为 10 -4

  DOI：

  10.3389/fphar.2022.868545
• 作为产物：
  描述：

  异烟肼 、 4-苯氧基苯甲醛 以 乙醇 、 水 为溶剂， 反应 24.0h， 以77%的产率得到N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity

  摘要：

  The disturbing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has been driving the scientific community to urgently search for new and efficient antitubercular drugs. Despite the various drugs currently under evaluation, isoniazid is still the key and most effective component in all multi-therapeutic regimens recommended by the WHO. This paper describes the QSAR-oriented design, synthesis and in vitro antitubercular activity of several potent isoniazid derivatives (isonicotinoyl hydrazones and isonicotinoyl hydrazides) against H37Rv and two resistant Mtb strains. QSAR studies entailed RFs and ASNNs classification models, as well as MLR models. Strict validation procedures were used to guarantee the models' robustness and predictive ability. Lipophilicity was shown not to be relevant to explain the activity of these derivatives, whereas shorter N-N distances and lengthy substituents lead to more active compounds. Compounds I, 2, 4, 5 and 6, showed measured activities against H37Rv higher than INH (i.e., MIC <= 0.28 mu M), while compound 9 exhibited a six fold decrease in MIC against the katG (S315T) mutated strain, by comparison with INH (Le., 6.9 vs. 43.8 mu M). All compounds were ineffective against H37Rv(INH) (Delta katG), a strain with a full deletion of the katG gene, thus corroborating the importance of KatG in the activation of INH-based compounds. The most potent compounds were also shown not to be cytotoxic up to a concentration 500 times higher than MIC. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.077

文献信息

• Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity
  作者：Filomena Martins、Susana Santos、Cristina Ventura、Ruben Elvas-Leitão、Lídia Santos、Susana Vitorino、Marina Reis、Vanessa Miranda、Henrique F. Correia、João Aires-de-Sousa、Vasyl Kovalishyn、Diogo A.R.S. Latino、Jorge Ramos、Miguel Viveiros

  DOI：10.1016/j.ejmech.2014.04.077

  日期：2014.6

  The disturbing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has been driving the scientific community to urgently search for new and efficient antitubercular drugs. Despite the various drugs currently under evaluation, isoniazid is still the key and most effective component in all multi-therapeutic regimens recommended by the WHO. This paper describes the QSAR-oriented design, synthesis and in vitro antitubercular activity of several potent isoniazid derivatives (isonicotinoyl hydrazones and isonicotinoyl hydrazides) against H37Rv and two resistant Mtb strains. QSAR studies entailed RFs and ASNNs classification models, as well as MLR models. Strict validation procedures were used to guarantee the models' robustness and predictive ability. Lipophilicity was shown not to be relevant to explain the activity of these derivatives, whereas shorter N-N distances and lengthy substituents lead to more active compounds. Compounds I, 2, 4, 5 and 6, showed measured activities against H37Rv higher than INH (i.e., MIC <= 0.28 mu M), while compound 9 exhibited a six fold decrease in MIC against the katG (S315T) mutated strain, by comparison with INH (Le., 6.9 vs. 43.8 mu M). All compounds were ineffective against H37Rv(INH) (Delta katG), a strain with a full deletion of the katG gene, thus corroborating the importance of KatG in the activation of INH-based compounds. The most potent compounds were also shown not to be cytotoxic up to a concentration 500 times higher than MIC. (C) 2014 Elsevier Masson SAS. All rights reserved.
• In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis
  作者：Joaquim Trigo Marquês、Catarina Frazão De Faria、Marina Reis、Diana Machado、Susana Santos、Maria da Soledade Santos、Miguel Viveiros、Filomena Martins、Rodrigo F. M. De Almeida

  DOI：10.3389/fphar.2022.868545

  日期：——

  compounds with a good performance concerning several in vitro assays, their cytotoxicity against human liver HepG2 cells was determined and their ability to bind human serum albumin was thoroughly investigated. For the two new derivatives presented in this study, we also determined their lipophilicity and activity against both the wild type and an isoniazid-resistant strain of Mycobacterium tuberculosis

  耐多药结核病的高发加剧了到2030年结束这一流行病的挑战。2020年因结核病死亡的人数比2019年增加，新发现的耐多药结核病病例稳定接近3% . 这种背景激发了对新的和更有效的抗结核化合物的研究，最终导致了面向 QSAR 的设计和合成一系列对抗结核有活性的异烟肼衍生物。结核分枝杆菌. 由此，本工作研究了一些有前景的异烟酰腙和异烟酰肼。评估化学衍生化是否产生具有良好性能的化合物体外测定，确定了它们对人肝HepG2细胞的细胞毒性，并彻底研究了它们结合人血清白蛋白的能力。对于本研究中提出的两种新衍生物，我们还确定了它们对野生型和异烟肼抗性菌株的亲脂性和活性。结核分枝杆菌携带最普遍的突变卡特格基因，S315T。所有化合物的细胞毒性都低于临床使用的许多药物，72 小时攻击后的 IC 50值始终高于 25 µM。此外，所研究的所有异烟肼衍生物与人血清白蛋白的结合比异烟肼本身更强，解离常数分别为 10 -4