(Z)-1-ethyl-7-methyl-4-oxo-N'-(2-oxoindolin-3-ylidene)-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide | 1253047-23-2

• 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: (Z)-1-ethyl-7-methyl-4-oxo-N'-(2-oxoindolin-3-ylidene)-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide
• CAS: 1253047-23-2
• 化学式: C₂₀H₁₇N₅O₃
• 分子量: 375.387
• InChiKey: ZTMAZUHTOFLFPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.81
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  105.45
• 氢给体数：
  2.0
• 氢受体数：
  6.0

文献信息

• 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.