nalidixic acid | 944441-96-7

• 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
• 英文别名: Ethoxycarbonyl 1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylate
• CAS: 944441-96-7
• 化学式: C₁₅H₁₆N₂O₅
• 分子量: 304.302
• InChiKey: VSGPBWZYAYYTNK-UHFFFAOYSA-N

物化性质

• 沸点：
  429.8±55.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  nalidixic acid 在 一水合肼 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-{2-[(4,5,6,7-tetrachloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)amino]-1-isopropyl-2-oxo-ethyl}-1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Synthesis and Reactions of New Chiral Linear Carboxamides with an Incorporated Peptide Linkage Using Nalidixic Acid and Amino Acids as Starting Materials

  摘要：

  4b 通过将 1-乙基-1,4-二氢-7-甲基-4-氧代-喹啉-3-羧酸（萘啶酸，1）与适当的氨基酸甲酯偶联，制备了一系列具有肽键的手性线性羧酰胺衍生物（2- 15）。1 与氨基酸甲酯偶联后得到相应的肽甲酯 2，用甲醇氢氧化钠将其水解为相应的酸 3。用肼水合物对酯 2 进行肼解，可得到相应的酸肼衍生物 4。后一种化合物与适当的醛或苯乙酮衍生物偶联，分别得到相应的希夫碱衍生物 5 和 6。酰肼衍生物与异硫氰酸苯酯或羰基衍生物反应，分别得到相应的硫代氨基甲酰肼 7 和化合物 8-10。此外，4b 与酸单酸酐处理后可得到相应的亚胺衍生物 11-13。最后，4b 与四羧酸二酐衍生物反应，得到相应的二亚氨基羧酰胺衍生物 14 和 15。

  DOI：

  10.5560/znb.2014-3282
• 作为产物：
  描述：

  {[(6-甲基-2-吡啶基)氨基]亚甲基}丙二酸二乙酯 在 sodium hydroxide 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二苯醚 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 nalidixic acid
  参考文献：
  名称：

  Synthesis of Selected Novel Covalently Linked Flavoquinolones

  摘要：

  描述了通过混合酸酐法合成新型共价连接的黄酮喹诺酮类化合物，并通过紫外/可见光谱和1H核磁共振光谱数据进行了其光谱学研究。

  DOI：

  10.1055/s-2005-870019

文献信息

• Synthesis and release kinetics of polymerisable ester drug conjugates: towards pH-responsive infection-resistant urinary biomaterials
  作者：Colin P. McCoy、Nicola J. Irwin、Christopher Brady、David S. Jones、Gavin P. Andrews、Sean P. Gorman

  DOI：10.1016/j.tetlet.2013.03.020

  日期：2013.5

  Herein we report the synthesis, characterisation and hydrolytic release kinetics of a suite of novel, polymerisable ester quinolone conjugates with varying alkenyl chain lengths. Hydrolysis was shown to proceed up to 17-fold faster upon elevation of pH from neutral to pH 9.29, making these conjugates attractive for the development of 'designer' infection-resistant urinary biomaterials exploiting the increase in urine pH reported at the onset of catheter-associated infection to trigger drug release. (C) 2013 Elsevier Ltd. All rights reserved.
• Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building
  作者：Tarek Aboul-Fadl、Fayzah A.S. Bin-Jubair、Omima Aboul-Wafa

  DOI：10.1016/j.ejmech.2010.07.020

  日期：2010.10

  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.
• Aboul-Fadl; Fouad, Pharmazie, 1996, vol. 51, # 1, p. 30 - 33
  作者：Aboul-Fadl、Fouad

  DOI：——

  日期：——
• Synthesis and in vitro evaluation of ferutinol aryl esters for estrogenic activity and affinity toward cannabinoid receptors
  作者：Ahmed M. Galal Osman、Ehab A. Abourashed、Desmond Slade、Safwat A. Ahmed、Waseem Gul、Shabana I. Khan、Tarek Abo Elfadl、Olivia R. Dale、Afeef S. Husni、Stephen J. Cutler、Mahmoud A. ElSohly

  DOI：10.1007/s00044-015-1319-7

  日期：2015.6

  Ferutinin (1), the major constituent of Ferula hermonis and other Ferula species, is a sesquiterpene ester with remarkable estrogenic activity, beside other valuable medicinal properties. To investigate the influence of chemical modification of the ferutinin structure on its estrogenic effect and binding affinity toward the cannabinoid CB1 and CB2 receptors, twelve derivatives of 1 were prepared and evaluated in vitro, together with the parent compound, for the respective bioactivities, based on the recent evidence for estrogen-endocannabinoid interaction. Nine of the prepared derivatives (3-11) are new semisynthetic esters of 1. The parent compound ferutinin (1) exhibited the highest level of estrogenic activity (EC50 0.3 mu M and a percent maximal 17 beta-estradiol response of 90 % at 1 A mu M). Compound 6 was found to be a selective agonist for CB2 receptor (EC50 0.051 mu M, Ki 0.025 mu M), with much less affinity for CB1 receptor (EC50 97 mu M, Ki 48.5 mu M). Compound 8 was a selective agonist for CB1 (EC50 62, Ki 0.031 mu M) with no affinity toward CB2.
• Synthesis and Reactions of New Chiral Linear Carboxamides with an Incorporated Peptide Linkage Using Nalidixic Acid and Amino Acids as Starting Materials
  作者：Nagy M. Khalifa、Ahmed M. Naglah、Mohamed A. Al-Omar、Mohamed H. Abo-Ghalia、Abd El-Galil E. Amr

  DOI：10.5560/znb.2014-3282

  日期：2014.3.1

  A series of chiral linear carboxamide derivatives (2- 15) with an incorporated peptide linkage have been prepared via the coupling of 1-ethyl-1,4-dihydro-7-methyl-4-oxo-quinoline-3-carboxylic acid (nalidixic acid, 1) with appropriate amino acid methyl esters. Coupling of 1 with amino acid methyl esters gave the corresponding peptide methyl esters 2, which were hydrolyzed with methanolic sodium hydroxide to the corresponding acids 3. Hydrazinolysis of esters 2with hydrazine hydrate afforded the corresponding acid hydrazide derivatives 4. The latter compounds were coupled with appropriate aldehydes or acetophenone derivatives to afford the corresponding Schiff base derivatives 5 and 6, respectively. The hydrazide derivative was reacted with phenyl isothiocyanate or carbonyl derivatives to give the corresponding thiosemicarbazide 7 and compounds 8- 10, respectively. Also, 4b was treated with acid monoanhydrides to give the corresponding imide derivatives 11- 13. Finally, 4b was reacted with tetracarboxylic acid dianhydride derivatives to afford the corresponding diimido carboxamide derivatives 14 and 15

  4b 通过将 1-乙基-1,4-二氢-7-甲基-4-氧代-喹啉-3-羧酸（萘啶酸，1）与适当的氨基酸甲酯偶联，制备了一系列具有肽键的手性线性羧酰胺衍生物（2- 15）。1 与氨基酸甲酯偶联后得到相应的肽甲酯 2，用甲醇氢氧化钠将其水解为相应的酸 3。用肼水合物对酯 2 进行肼解，可得到相应的酸肼衍生物 4。后一种化合物与适当的醛或苯乙酮衍生物偶联，分别得到相应的希夫碱衍生物 5 和 6。酰肼衍生物与异硫氰酸苯酯或羰基衍生物反应，分别得到相应的硫代氨基甲酰肼 7 和化合物 8-10。此外，4b 与酸单酸酐处理后可得到相应的亚胺衍生物 11-13。最后，4b 与四羧酸二酐衍生物反应，得到相应的二亚氨基羧酰胺衍生物 14 和 15。