1-benzylidene-2-(4-(4-fluorophenyl)thiazol-2-yl)hydrazine | 325995-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-benzylidene-2-(4-(4-fluorophenyl)thiazol-2-yl)hydrazine
• 英文别名: 1-benzylidene-2-[4-(4-fluorophenyl)thiazol-2-yl]hydrazine；N-(benzylideneamino)-4-(4-fluorophenyl)-1,3-thiazol-2-amine
• CAS: 325995-62-8
• 化学式: C₁₆H₁₂FN₃S
• mdl: MFCD01532303
• 分子量: 297.356
• InChiKey: AQFCLUWFFGVKHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯甲醛 在 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 1-benzylidene-2-(4-(4-fluorophenyl)thiazol-2-yl)hydrazine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of some novel benzylidene-2-(4-phenylthiazol-2-yl) hydrazines as potential anti-inflammatory agents

  摘要：

  A series of substituted benzylidene-2-(4-phenylthiazol-2-yl) hydrazines (2a-q) have been synthesized, characterized and evaluated for their anti-inflammatory activity by carrageenin-induced hind paw edema (acute inflammation) and cotton pellet granuloma (chronic inflammation) methods in rats. In carrageenin-induced hind paw edema method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg(-1) body weight, p.o. showed excellent inhibitions (51.80-86.74 %) in between 1 and 4 h. Similarly, in cotton pellet granuloma method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg(-1) body weight, p.o. inhibited the granuloma formation (71.71-90.19 % inhibition) which was comparable to that of standard drug, ibuprofen (90.36 % inhibition of paw volume at 3 h and 94.02 % inhibition of granuloma formation). Structure activity relationship studies showed excellent activity of the compounds containing electron withdrawing group (fluoro, chloro, bromo or nitro) in phenyl ring at C2 and/or C4 position of thiazole ring.

  DOI：

  10.1007/s00044-013-0708-z

文献信息

• Synthesis and biological assessment of novel 2-thiazolylhydrazones and computational analysis of their recognition by monoamine oxidase B
  作者：Simona Distinto、Matilde Yáñez、Stefano Alcaro、M. Cristina Cardia、Marco Gaspari、M. Luisa Sanna、Rita Meleddu、Francesco Ortuso、Johannes Kirchmair、Patrick Markt、Adriana Bolasco、Gerhard Wolber、Daniela Secci、Elias Maccioni

  DOI：10.1016/j.ejmech.2011.12.027

  日期：2012.2

  Monoamine oxidase B (MAO-B) is a promising target for the treatment of neurodegenerative disorders. We report the synthesis and the biological evaluation of halogenated derivatives of 1-aryliden-2-(4-phenylthiazol-2-yl)hydrazines. The fluorinated series shows interesting activity and great selectivity toward the human recombinant MAO-B isoform expressed in baculovirus infected BTI insect cells. The multiple crystal structures alignment of the enzyme highlighted pronounced induced fit (IF) adaptations with respect to bound ligands. Therefore, IF docking (IFD) experiments and molecular dynamic (MD) simulations were carried out to reveal the putative binding mode and to explain the experimentally observed differences in the activity of 1-(aryliden-2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazines. The importance of water molecules within the binding site was also investigated. These are known to play an important role in the binding site cavity and to mediate protein ligand interactions. Detailed analyses of the trajectories provide insights on the chemical features required for the activity of this scaffold. In particular it was highlighted the importance of fluorine atom interacting with the water close to the cofactor and the influence of steric bulkiness of substituents in the arylidene moiety. Free energy perturbation (FEP) analysis confirmed experimental data. The information we deduced will help to develop novel high-affinity MAO-B inhibitors. (C) 2011 Elsevier Masson SAS. All rights reserved.