6-bromo-naphthalene-2-carboxylic acid (3,5-dibromo-2,4-dihydroxy-benzylidene)-hydrazide | 1147840-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-bromo-naphthalene-2-carboxylic acid (3,5-dibromo-2,4-dihydroxy-benzylidene)-hydrazide
• 英文别名: 6-bromo-N'-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-naphthohydrazide
• CAS: 1147840-51-4
• 化学式: C₁₈H₁₁Br₃N₂O₃
• 分子量: 543.009
• InChiKey: LDEONHKKHKVPNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.92
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  6-溴-2-萘甲酸甲酯 在 hydrazine hydrate 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 6.0h， 生成 6-bromo-naphthalene-2-carboxylic acid (3,5-dibromo-2,4-dihydroxy-benzylidene)-hydrazide
  参考文献：
  名称：

  Discovery and Mechanism Study of SIRT1 Activators that Promote the Deacetylation of Fluorophore-Labeled Substrate

  摘要：

  SIRT1 is an NAD(+)-dependent deacetylase, whose activators have potential therapeutic applications in age-related diseases. Here we report a new class of SIRT1 activators. The activation is dependent on the fluorophore labeled to the substrate. To elucidate the activation mechanism, we solved the crystal structure of SIRT3/ac-RHKKac-AMC complex. The structure revealed that the fluorophore blocked the H-bond formation and created a cavity between the substrate and the Rossmann fold. We built the SIRT1/ac-RHKKac-AMC complex model based on the crystal structure. K-m and K-d determinations demonstrated that the fluorophore decreased the peptide binding affinity. The binding modes of SIRT1 activators indicated that a portion of the activators interacts with the fluorophore through pi-stacking, while the portion inserts into the cavity or interacts with the Rossmann fold, thus increasing the substrate affinity. Our study provides new insights into the mechanism of SIRT1 activation and may aid the design of novel SIRT1 activators.

  DOI：

  10.1021/jm301032j

文献信息

• Discovering Potent Inhibitors Against the β-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) of <i>Helicobacter pylori</i>: Structure-Based Design, Synthesis, Bioassay, and Crystal Structure Determination
  作者：Lingyan He、Liang Zhang、Xiaofeng Liu、Xianghua Li、Mingyue Zheng、Honglin Li、Kunqian Yu、Kaixian Chen、Xu Shen、Hualiang Jiang、Hong Liu

  DOI：10.1021/jm8015602

  日期：2009.4.23

  The discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening.