nalidixic acid hydrazide | 79878-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: nalidixic acid hydrazide
• 英文别名: 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide；1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carbohydrazide；1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carbohydrazide
• CAS: 79878-27-6
• 化学式: C₁₂H₁₄N₄O₂
• mdl: MFCD07065509
• 分子量: 246.269
• InChiKey: LTXFNOZRVDFIKB-UHFFFAOYSA-N

物化性质

• 熔点：
  184.2-186.0 °C
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  nalidixic acid hydrazide 在 盐酸 、 三乙胺 、 sodium nitrite 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-[4-[(1-ethyl-7-methyl-4-oxo-1,8-naphthyridin-3-yl)amino]pentyl]isoindole-1,3-dione
  参考文献：
  名称：

  萘啶酮衍生物的合成作为潜在的抗疟药

  摘要：

  在本文中，我们介绍了8-（4'-氨基-1'甲基-丁基氨基）-5-（β，β，β-三氟乙氧基）-1,6-萘啶（4），8-（4'-氨基-1'甲基丁基氨基）-6-甲基-1,6-萘基甲基-5-一个（5），两个1-烷基-3-（4'-氨基-1'-甲基丁基氨基）-7-甲基-1,8 -萘啶-4-酮（20a）和20b），3-（1'-氨基-4'-甲基丁基-氨基）-1-乙基-7-甲基-1,8-萘啶-4-酮（20c），和4-（4'-二乙基氨基-1'-甲基丁基氨基）-7-甲基-1,7-萘啶-8-一（28）。在伯氏疟原虫筛查中评估了化合物的抗疟活性，发现该化合物无活性。

  DOI：

  10.1002/jhet.5570180519
• 作为产物：
  描述：

  nalidixic acid 在 肼 作用下， 反应 4.0h， 生成 nalidixic acid hydrazide
  参考文献：
  名称：

  Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building

  摘要：

  Tuberculosis (TB) remains among the world's great public health challenges. Worldwide resurgence of TB is due to two major problems. the AIDS epidemic, which started in the mid-1980s, and the outbreak of multidrug resistant (MDR) TB. Thus, there is an urgent need for anti-TB drugs with enhanced activity against MDR strains. In recent years, Schiff bases of 1H-indole-2,3-diones are reported to exhibit anti-TB activity On the other hand, several quinolone antibacterial agents have been examined as inhibitors of TB. as well as other mycobacterial infections. Accordingly, the current work involved design and synthesis of Schiff bases of nalidixic acid carbohydrazide and Isatin derivatives (5,6a-f and 7,8a-c). Structures of the synthesized derivatives were confirmed on the bases of spectral methods of analyses. Anti-TB activity of the synthesized derivatives was investigated against four Mycobacterium strains. Mycobacterium intercellulari, Mycobacterium xenopi, Mycobacterium cheleneo and Mycobacterium smegmatis. Modest anti-TB activity was observed within the investigated compounds, however, compound 5f revealed potent anti-TB activity with MIC 0.625 mu g/ml, which is 20 times greater than the reference drug isoniazid, INH, (MIC = 12.5 mu g/ml). A hypothetical pharmacophore model was built using Molecular Operating Environment (MOE) program and 10 compounds structurally related to the synthesized ones with reported anti-TB activity. The Pharmacophonc model built revealed the necessity of the following pharmacophoric features for anti-TB activity: aromatic center, hydrogen bond acceptor/metal ligator center, hydrogen bond donor center and aromatic center/hydrophobic area. Theses features were consistent with the found anti-TB activity of the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.020

文献信息

• Synthesis, characterization, DNA interactions, DNA cleavage, radical scavenging activity, antibacterial, anti-proliferative and docking studies of new transition metal complexes
  作者：Kishan Prasad Chennam、Mudavath Ravi、B. Ushaiah、V. Srinu、Ravi Kumar Eslavath、Ch. Sarala Devi

  DOI：10.1007/s10895-015-1701-3

  日期：2016.1

  The compound N-(2-hydroxybenzylidene)-1-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8 naphthyridine-3-carbohydrazide (LH) and its Cu (II), Co (II) and Zn (II) complexes were synthesized and characterized. The absorption spectral titrations and competitive DNA binding studies depicted those complexes of title compound bind to CT-DNA through intercalation. Interestingly [Cu (II)-(L2)] showed relatively high binding constant value (6.61 x 105 M−1) compared to [Co (II)-(L2)] (4.378× 105 M−1) and [Zn (II)-(L2)] (3.1x105 M−1). Ligand and its complexes were also examined for DNA nuclease activity against pBR-322 plasmid DNA, which showed that [Cu (II)-(L2)] had the best hydrolytic cleavage property displaying prominent double-strand DNA cleavage. In addition, antioxidant activities of the ligand and its metal complexes investigated through scavenging effects for DPPH radical in- vitro, indicated their potentiality as good antioxidants. The in vitro anti-bacterial study inferred the better anti-bacterial activity of [Cu (II)-(L2)] and this was also correlated theoretically by employing docking studies wherein [Cu (II)-(L2)] displayed good Gold score and Chem score. Finally the in vitro anti- proliferative activity of studied compounds was tested against HeLa and MCF-7 cell lines. Interestingly [Cu (II)-(L2)] displayed lower IC50 value and lower percentage of viability in both HeLa and MCF-7 cell lines.

  化合物N-(2-羟基苯亚甲基)-1-乙基-1,4-二氢-7-甲基-4-氧代-1,8-萘啶-3-甲酰肼(LH)及其Cu(II)、Co(II)和Zn(II)配合物被合成并进行了表征。吸收光谱滴定和竞争性DNA结合研究表明，该化合物的配合物通过插入方式结合到CT-DNA。有趣的是，与[Co(II)-(L2)](4.378×105 M−1)和[Zn(II)-(L2)](3.1×105 M−1)相比，[Cu(II)-(L2)]显示出相对较高的结合常数值(6.61×105 M−1)。对配体及其配合物进行了针对pBR-322质粒DNA的DNA核酸酶活性检测，结果显示[Cu(II)-(L2)]具有最佳的水解切割性能，能够显著地切割双链DNA。此外，通过体外DPPH自由基清除效果研究了配体及其金属配合物的抗氧化活性，表明它们具有良好的抗氧化潜力。体外抗菌研究推断出[Cu(II)-(L2)]具有较好的抗菌活性，并通过分子对接研究得到理论验证，其中[Cu(II)-(L2)]显示出良好的Gold评分和Chem评分。最后，对研究化合物进行了针对HeLa和MCF-7细胞系的体外抗增殖活性测试。有趣的是，[Cu(II)-(L2)]在HeLa和MCF-7细胞系中显示出较低的IC50值和存活率百分比。
• Spectro Analytical, Computational and In Vitro Biological Studies of Novel Substituted Quinolone Hydrazone and it’s Metal Complexes
  作者：Narsimha Nagula、Sudeepa Kunche、Mohmed Jaheer、Ravi Mudavath、Sreekanth Sivan、Sarala Devi Ch

  DOI：10.1007/s10895-017-2185-0

  日期：2018.1

  Quantum mechanical parameters, contour maps of highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) and corresponding binding energy values were computed using semi empirical single point PM3 method. The stoichiometric equilibrium studies of metal complexes carried out spectrophotometrically using Job’s continuous variation and mole ratio methods inferred formation

  萘啶酸的一些新型过渡金属[Cu（II），Ni（II）和Co（II）]配合物已经制备，并通过光谱分析技术进行了表征，即元素分析，1 H-NMR，质量，UV–可见光，红外，TGA-DTA，SEM-EDX，ESR和分光光度法研究。HyperChem 7.5软件用于分子和离子形式的标题化合物的几何优化。使用半经验单点PM3方法计算了量子力学参数，最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）的等高线图以及相应的结合能值。使用乔布的连续变化和摩尔比方法分光光度法进行的金属配合物的化学计量平衡研究推断形成了1：2（ML2）各自系统中的金属络合物。筛选了具有抗菌和抗真菌特性的标题化合物及其金属配合物，证明了金属配合物中活性的提高。核酸酶切割CT-DNA的活性和MTT测定涉及金属配合物的体外细胞毒性的研究显示出高活性。另外，通过电子吸收和荧光测量研究的Cu（II），Ni（II）和Co（II）
• Environment Friendly Synthesis of <i>N</i>′-(1,3-Diphenylallylidene)-1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazides: Crystal Structure and Their Anti-oxidant Potential
  作者：Shafaq Mubarak、Muhammad Zia-Ur-Rehman、Nadia Jamil、Muhammad Zaheer、Muhammad Nadeem Arshad、Abdullah Mohammad Asiri

  DOI：10.1248/cpb.c19-00478

  日期：2019.11.1

  An environment friendly synthesis of novel hybrid pharmacophores derived from synergism of nalidixic acid and 1,3-diphenylprop-2-en-1-ones is described. Percent yield and reaction times of microwave assisted reactions have been compared with the reactions carried out under conventional reaction conditions which show marked decrease in reaction times and significant increase in yields. Besides, anti-oxidant

  描述了一种环境友好的合成方法，该方法由萘啶酸和1,3-二苯基丙-2-烯-1-酮的协同作用衍生而来。已经将微波辅助反应的产率和反应时间与在常规反应条件下进行的反应进行了比较，所述反应在反应时间上显着减少并且产率显着增加。此外，对合成的杂化化合物的抗氧化能力进行了评估，其中一些化合物表现出明显的抗坏血酸当量三价铁还原抗氧化剂能力（FRAP）和金属螯合能力。还介绍了合成系列的一个代表的晶体研究。
• Synthesis, antimicrobial evaluation and QSAR analysis of novel nalidixic acid based 1,2,4-triazole derivatives
  作者：Nisha Aggarwal、Rajesh Kumar、Prem Dureja、J.M. Khurana

  DOI：10.1016/j.ejmech.2011.06.009

  日期：2011.9

  was emerged as promising antimicrobial agent (MIC = 16 μg/mL). Quantitative structure activity relationship (QSAR) analysis was carried out using various distance-based topological indices, steric and hydrophobic parameters. Based on the QSAR analysis it is indicative that lipophilic and steric parameters are the pre-requisites for these molecules to act as potent antimicrobial agents.

  合成了新的基于萘啶酸的1,2,4-三唑衍生物，并使用诸如1 H NMR，13 C NMR，IR和质谱的光谱技术对其进行了表征。筛选所有这些化合物对五种细菌和两种病原性真菌的抗菌活性。这些化合物中的大多数显示出比母体化合物4-氨基-5-巯基-1,2,4-三唑更好的抗菌活性。在所有筛选的化合物中，3- 6-（2-氯苯基）-1,2,4-三唑[3,4- -b ] [1,3,4]噻二唑-3-基} -1-乙基-7 -甲基-1,8-萘啶-4（1 H）-一（23）成为有前途的抗菌剂（MIC = 16μg/ mL）。使用各种基于距离的拓扑指数，空间和疏水参数进行了定量结构活性关系（QSAR）分析。基于QSAR分析，表明亲脂性和空间参数是这些分子充当有效抗菌剂的前提。
• Synthesis of Novel Nalidixic Acid-Based 1,3,4-Thiadiazole and 1,3,4-Oxadiazole Derivatives as Potent Antibacterial Agents
  作者：Nisha Aggarwal、Rajesh Kumar、Prem Dureja、Jitender Mohan Khurana

  DOI：10.1111/j.1747-0285.2011.01316.x

  日期：2012.4

  acid‐based 1,3,4‐thia(oxa)diazoles, their thio ethers, sulfones, bis mercapto, and Mannich bases were synthesized and characterized by Infrared spectra, 1H NMR, 13C NMR, and elemental analysis. These compounds were evaluated for their antibacterial activity against two Gram‐positive and three Gram‐negative bacteria. The preliminary bioassay showed that most of the compounds had better antibacterial activity

  基于红外光谱，1 H NMR，13 C NMR和元素分析合成了新颖的基于萘啶酸的1,3,4-噻二（恶唑）二唑，其硫醚，砜，双巯基和曼尼希碱。评估了这些化合物对两种革兰氏阳性和三种革兰氏阴性细菌的抗菌活性。初步的生物分析表明，大多数化合物对五种试验细菌的剂量为50μg/ mL时，其母体化合物1,3,4-噻吩二恶唑的抗菌活性均优于母体化合物。基于萘啶酸的1,3,4-噻二唑的四个曼尼希碱对枯草芽孢杆菌，肺炎克雷伯菌和铜绿假单胞菌的最低抑制浓度在6.25–125μg/ mL范围内。