6-(aminomethyl)pyrimidin-4-ol | 933756-94-6

• 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: 6-(aminomethyl)pyrimidin-4-ol
• 英文别名: 6-(Aminomethyl)pyrimidin-4-ol；4-(aminomethyl)-1H-pyrimidin-6-one
• CAS: 933756-94-6
• 化学式: C₅H₇N₃O
• 分子量: 125.13
• InChiKey: VYOICLJSGPUPPE-UHFFFAOYSA-N

物化性质

• 沸点：
  245.9±42.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(aminomethyl)pyrimidin-4-ol 、 5-氯-3-((3,5-二甲基苯基)磺酰基)-1H-吲哚-2-羧酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以23%的产率得到5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-N-((6-hydroxypyrimidin-4-yl)methyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains

  摘要：

  We designed and synthesized 21 new indolylarylsulfones (IASs) as new HIV-1 NNRTIs. Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC₅₀ = <0.7 nM; Y181C EC₅₀ = <0.7 nM; Y188L EC₅₀ = 21.3 nM; K103N-Y181C EC₅₀ = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs. Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N-Y181C RTs clarified a general binding mode that was consistent with biological results. Kinetic experiments disclosed that derivative 12 preferentially binds WT and K103N-Y181C RTs to binary and ternary complexes, respectively.

  DOI：

  10.1016/j.ejmech.2020.112696

文献信息

• New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains
  作者：Marianna Nalli、Jorge I. Armijos Rivera、Domiziana Masci、Antonio Coluccia、Roger Badia、Eva Riveira-Muñoz、Alessandro Brambilla、Elisabetta Cinquina、Ombretta Turriziani、Francesca Falasca、Myriam Catalano、Cristina Limatola、José A. Esté、Giovanni Maga、Romano Silvestri、Emmanuele Crespan、Giuseppe La Regina

  DOI：10.1016/j.ejmech.2020.112696

  日期：2020.12

  We designed and synthesized 21 new indolylarylsulfones (IASs) as new HIV-1 NNRTIs. Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC₅₀ = <0.7 nM; Y181C EC₅₀ = <0.7 nM; Y188L EC₅₀ = 21.3 nM; K103N-Y181C EC₅₀ = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs. Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N-Y181C RTs clarified a general binding mode that was consistent with biological results. Kinetic experiments disclosed that derivative 12 preferentially binds WT and K103N-Y181C RTs to binary and ternary complexes, respectively.