4-(pyridin-3-yl)benzohydrazide | 1421511-67-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(pyridin-3-yl)benzohydrazide
• 英文别名: 4-Pyridin-3-ylbenzohydrazide
• CAS: 1421511-67-2
• 化学式: C₁₂H₁₁N₃O
• 分子量: 213.239
• InChiKey: KSGKQSFZWQJBGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(pyridin-3-yl)benzohydrazide 、 3,5-二溴-2,4-二羟基苯甲醛 以 乙醇 、 溶剂黄146 为溶剂， 反应 3.0h， 以63%的产率得到N'-(3,5-dibromo-2,4-dihydroxybenzylidene)-4-(pyridin-3-yl)benzohydrazide
  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
• 作为产物：
  描述：

  3-溴吡啶 在 四(三苯基膦)钯 、 hydrazine hydrate 、 potassium fluoride dihydrate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 3.83h， 生成 4-(pyridin-3-yl)benzohydrazide
  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

• Identification of novel benzoyl hydrazine derivatives as activators of neddylation pathway to inhibit the tumor progression in vitro
  作者：Xuan Wang、Sumeng Guan、Zunming Tian、Mei Zhao、Mengyu Li、Hua Yang、Ling Zhu、Moran Sun

  DOI：10.1007/s00044-024-03193-4

  日期：2024.3

  against A549, MGC-803, MCF-7KYSE-30 cell lines. The cell-based mechanistic studies showed that IIb-10 bearing the benzoyl hydrazine motif can selectively inhibit the Neddylation modification of Cullin1 and Cullin3 by inhibiting NEDD8 activase and then, leads to a dose-dependent reduction in the level of UBC12-NEDD8 complex via interacting with NAE1 directly. Cellular mechanisms elucidated that compound

  Neddylation 修饰在许多类型的人类肿瘤中经常过度表达。因此，靶向neddylation途径已被确定为可行的抗癌治疗策略。 NEDD8 激活酶 (NAE) 在多种细胞功能中发挥着至关重要的作用。在这里，开发、生产了一个新的哌啶类似物文库，并评估了其对 A549、MGC-803、MCF-7KYSE-30 细胞系的抗增殖功效。基于细胞的机制研究表明，带有苯甲酰肼基序的IIb-10可以通过抑制 NEDD8 激活酶来选择性抑制 Cullin1 和 Cullin3 的 Neddylation 修饰，然后通过相互作用导致 UBC12-NEDD8 复合物水平呈剂量依赖性降低。直接与NAE1。细胞机制阐明化合物IIb-10能够使 MGC-803 细胞的细胞周期停止在 G2/M 期并引发细胞凋亡。总而言之，酰肼连接的哌啶衍生物可能是作为开发高效neddylation抑制剂的先导化合物的有前途的候选者。