pyrimidine-4,6-dicarbohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: pyrimidine-4,6-dicarbohydrazide
• 化学式: C₆H₈N₆O₂
• 分子量: 196.169
• InChiKey: ZOOQSWHSXRCYPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  pyrimidine-4,6-dicarbohydrazide 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成
  参考文献：
  名称：

  Novel cationic bis(acylhydrazones) as modulators of Epstein–Barr virus immune evasion acting through disruption of interaction between nucleolin and G-quadruplexes of EBNA1 mRNA

  摘要：

  The oncogenic Epstein-Barr virus (EBV) evades the immune system through limiting the expression of its highly antigenic and essential genome maintenance protein, EBNA1, to the minimal level to ensure viral genome replication, thereby also minimizing the production of EBNA1-derived antigenic peptides. This regulation is based on inhibition of translation of the virally-encoded EBNA1 mRNA, and involves the interaction of host protein nucleolin (NCL) with G-quadruplex (G4) structures that form in the glycine-alanine repeat (GAr)-encoding sequence of the EBNA1 mRNA. Ligands that bind to these G4-RNA can prevent their interaction with NCL, leading to disinhibition of EBNA1 expression and antigen presentation, thereby interfering with the immune evasion of EBNA1 and therefore of EBV (M.J. Lista et al., Nature Commun., 2017, 8, 16043). In this work, we synthesized and studied a series of 20 cationic bis(acylhydrazone) derivatives designed as G4 ligands. The in vitro evaluation showed that most derivatives based on central pyridine (Py), naphthyridine (Naph) or phenanthroline (Phen) units were efficient G4 binders, in contrast to their pyrimidine (Pym) counterparts, which were poor G4 binders due to a significantly different molecular geometry. The influence of lateral heterocyclic units (N-substituted pyridinium or quinolinium residues) on G4-binding properties was also investigated. Two novel compounds, namely PyDH2 and PhenDH2, used at a 5 μM concentration, were able to significantly enhance EBNA1 expression in H1299 cells in a GAr-dependent manner, while being significantly less toxic than the prototype drug PhenDC3 (GI₅₀ > 50 μM). Antigen presentation, RNA pull-down and proximity ligation assays confirmed that the effect of both drugs was related to the disruption of NCL-EBNA1 mRNA interaction and the subsequent promotion of GAr-restricted antigen presentation. Our work provides a novel modular scaffold for the development of G-quadruplex-targeting drugs acting through interference with G4-protein interaction.

  DOI：

  10.1016/j.ejmech.2019.05.042
• 作为产物：
  描述：

  嘧啶-4,6-二甲酸二甲酯 在 一水合肼 作用下， 以 甲醇 为溶剂， 生成 pyrimidine-4,6-dicarbohydrazide
  参考文献：
  名称：

  Pyrimidine-4,6-dicarboxylic acid diamides, processes for the use

  摘要：

  嘌呤-4,6-二羧酸二酰胺，其使用方法以及基于这些化合物的药物。本发明涉及公式I的嘌呤-4,6-二羧酸二酰胺，其中R.sup.1和R.sup.2具有所述含义。根据本发明的化合物抑制脯氨酸羟化酶和赖氨酸羟化酶，并可用作纤维抑制剂和免疫抑制剂。

  公开号：

  US05130317A1

文献信息

• NOVEL HYDRAZONE DERIVATIVES FOR PREVENTING OR TREATING EBV-RELATED CANCERS
  申请人：Université de Bretagne Occidentale

  公开号：EP3549938A1

  公开（公告）日：2019-10-09

  The present invention relates to novel bis-hydrazone derivatives of formula (I): wherein Ar1 and Ar2 may be identical or different and are each independently selected from the group consisting of groups of formula (II) and (III): Y1 and Z1 are independently CH or NRc+, provided that al least one of Y1 and Z1 is NRc+ and at least one of Y1 and Z1 is CH, and Ra, Rb, Rc, X2- and L as defined in the claims, or a hydrate or a solvate thereof. Compositions and kits comprising same are also described. Said bis-hydrazone derivatives of formula (I), compositions and kits are useful as drugs, in particular for treating or preventing cancers associated with the Epstein-Barr Virus.

  本发明涉及一种新的双酰肼衍生物，其化学式为（I）：其中Ar1和Ar2可以相同也可以不同，并且分别独立地选自化学式（II）和（III）的基团：Y1和Z1独立地为CH或NRc+，前提是Y1和Z1中至少有一个为NRc+，并且Y1和Z1中至少有一个为CH，以及在权利要求中定义的Ra、Rb、Rc、X2-和L，或者其水合物或溶剂化合物。还描述了包含上述化合物的组合物和试剂盒。所述的双酰肼衍生物的化学式（I）、组合物和试剂盒可用作药物，特别用于治疗或预防与EB病毒相关的癌症。
• Novel Hydrazone Derivatives For Preventing Or Treating EBV-Related Cancers
  申请人：Universite de Bretagne Occidentale

  公开号：US20210161887A1

  公开（公告）日：2021-06-03

  The present invention relates to novel bis-hydrazone derivatives of formula (I): wherein Ar 1 and Ar 2 may be identical or different and are each independently selected from the group consisting of groups of formula (II) and (III): Y 1 and Z 1 are independently CH or NR c + , provided that al least one of Y 1 and Z 1 is NR c + and at least one of Y 1 and Z 1 is CH, and R a , R b , R c , X 2− and L as defined in the claims, or a hydrate or a solvate thereof. Compositions and kits comprising same are also described. Said bis-hydrazone derivatives of formula (I), compositions and kits are useful as drugs, in particular for treating or preventing cancers associated with the Epstein-Barr Virus.
• US5130317A
  申请人：——

  公开号：US5130317A

  公开（公告）日：1992-07-14
• [EN] NOVEL HYDRAZONE DERIVATIVES FOR PREVENTING OR TREATING EBV-RELATED CANCERS<br/>[FR] NOUVEAUX DÉRIVÉS D'HYDRAZONE POUR LA PRÉVENTION OU LE TRAITEMENT DE CANCERS LIÉS AU VEB
  申请人：UNIV BRETAGNE OCCIDENTALE

  公开号：WO2019193071A1

  公开（公告）日：2019-10-10

  The present invention relates to novel bis-hydrazone derivatives of formula (I) wherein Ar1 and Ar2 may be identical or different and are each independently selected from the group consisting of groups of formula (II) and (III) Y1 and Z1 are independently CH or NRC+, provided that al least one of Y1 and Z1 is NRc+ and at least one of Y1 and Z1 is CH, and Ra, Rb, Rc, X2- and L as defined in the claims, or a hydrate or a solvate thereof. Compositions and kits comprising same are also described. Said bis-hydrazone derivatives of formula (I), compositions and kits are useful as drugs, in particular for treating or preventing cancers associated with the Epstein-Barr Virus.

表征谱图