Diethyl benzene-1,4-diformamidate dihydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Diethyl benzene-1,4-diformamidate dihydrochloride
• 英文别名: diethyl benzene-1,4-dicarboximidate;dihydrochloride
• 化学式: C12H18Cl2N2O2
• mdl: MFCD00972178
• 分子量: 293.19
• InChiKey: LERRLALERRQDNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.65
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

文献信息

• Multivalent ligand for myotonic dystrophy
  申请人：The Board of Trustees of the University of Illinois

  公开号：US11242326B2

  公开（公告）日：2022-02-08

  Abnormally long r(CUG)n repeat expansion is believed to be the major cause of Myotonic dystrophy type 1 (DM1) because it binds to muscleblind-like 1 (MBNL 1) protein which regulates RNA splicing, leading to the mis-splicing of more than 100 pre-mRNAs. The rational design of oligomers with alternating bisamidine and melamine structure resulted in good binding affinity to the RNA target because of a multivalent effect. The oligomers also showed excellent activity in disrupting nuclear foci, reversing the mis-splicing of IR minigene, and sabotaging the toxic RNA biosynthesis. Excellent activity in Drosophila based DM1 models was also observed for the oligomers, rescuing the climbing ability of the flies upon oral treatment.

  异常长的r(CUG)n重复扩增被认为是1型肌营养不良症（DM1）的主要病因，因为它与调节RNA剪接的类肌球蛋白1（MBNL 1）结合，导致100多种前mRNA的错误剪接。通过合理设计具有双脒和三聚氰胺交替结构的低聚物，可产生多价效应，从而与 RNA 靶标产生良好的结合亲和力。这些寡聚物在破坏核病灶、逆转 IR 小基因的错误剪接以及破坏有毒 RNA 的生物合成方面也表现出了卓越的活性。在基于果蝇的 DM1 模型中，寡聚物也表现出卓越的活性，经口服治疗后，果蝇的攀爬能力得到了恢复。
• A MULTIVALENT LIGAND FOR MYOTONIC DYSTROPHY
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20200399231A1

  公开（公告）日：2020-12-24

  Abnormally long r(CUG)n repeat expansion is believed to be the major cause of Myotonic dystrophy type 1 (DM1) because it binds to muscleblind-like 1 (MBNL 1) protein which regulates RNA splicing, leading to the mis-splicing of more than 100 pre-mRNAs. The rational design of oligomers with alternating bisamidine and melamine structure resulted in good binding affinity to the RNA target because of a multivalent effect. The oligomers also showed excellent activity in disrupting nuclear foci, reversing the mis-splicing of IR minigene, and sabotaging the toxic RNA biosynthesis. Excellent activity in Drosophila based DM1 models was also observed for the oligomers, rescuing the climbing ability of the flies upon oral treatment.
• [EN] A MULTIVALENT LIGAND FOR MYOTONIC DYSTROPHY<br/>[FR] LIGAND MULTIVALENT POUR DYSTROPHIE MYOTONIQUE
  申请人：UNIV ILLINOIS

  公开号：WO2019040750A1

  公开（公告）日：2019-02-28

  Abnormally long r(CUG)n repeat expansion is believed to be the major cause of Myotonic dystrophy type 1 (DM1) because it binds to muscleblind-like 1 (MBNL1) protein which regulates RNA splicing, leading to the mis-splicing of more than 100 pre-mRNAs. The rational design of oligomers with alternating bisamidine and melamine structure resulted in good binding affinity to the RNA target because of a multivalent effect. The oligomers also showed excellent activity in disrupting nuclear foci, reversing the mis-splicing of IR minigene, and sabotaging the toxic RNA biosynthesis. Excellent activity in Drosophila based DM1 models was also observed for the oligomers, rescuing the climbing ability of the flies upon oral treatment.