1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐 | 34386-73-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐
• 英文名称: 1-(2-aminoethyl)pyrimidine-2,4(1H,3H)dione hydrogen chloride
• 英文别名: 1-(2-aminoethyl)uracil hydrochloride；1-(2-Amino-ethyl)-1h-pyrimidine-2,4-dione hydrochloride；1-(2-aminoethyl)pyrimidine-2,4-dione;hydrochloride
• CAS: 34386-73-7
• 化学式: C₆H₉N₃O₂*ClH
• 分子量: 191.617
• InChiKey: DCSPEUZFLLWUOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.08
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((2-chloropyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 、 1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以49.4%的产率得到4-((2-((2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047
• 作为产物：
  描述：

  tert-butyl (2-(3-benzoyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以68.1%的产率得到1-(2-氨基-乙基)-1H-嘧啶-2,4-二酮盐酸盐
  参考文献：
  名称：

  Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization

  摘要：

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.047

文献信息

• [EN] SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION<br/>[FR] PETITES MOLÉCULES DIRIGÉES CONTRE LE CÉRÉBLON POUR AMÉLIORER LA FONCTION DES LYMPHOCYTES T EFFECTEURS
  申请人：H LEE MOFFITT CANCER CENTER & RES INST INC

  公开号：WO2017161119A1

  公开（公告）日：2017-09-21

  Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.

  披露了针对小脑蛋白以增强效应T细胞功能的小分子。还披露了制造这些分子的方法以及使用它们治疗各种疾病状态的方法。
• Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization
  作者：Heng Zhang、Ye Tian、Dongwei Kang、Zhipeng Huo、Zhongxia Zhou、Huiqing Liu、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2017.02.047

  日期：2017.4

  A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based molecular hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound 16d showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that 16d was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility. The molecular modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. (C) 2017 Elsevier Masson SAS. All rights reserved.