N-(cyclohexylmethyl)-5,6-dihydroxy-2-phenylpyrimidine-4-carboxamide | 1407174-91-7

• 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: N-(cyclohexylmethyl)-5,6-dihydroxy-2-phenylpyrimidine-4-carboxamide
• 英文别名: N-(cyclohexylmethyl)-5-hydroxy-6-oxo-2-phenyl-1H-pyrimidine-4-carboxamide
• CAS: 1407174-91-7
• 化学式: C₁₈H₂₁N₃O₃
• 分子量: 327.383
• InChiKey: BTGSJEMKLAQJSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  95.34
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  环己甲胺 、 5,6-二羟基-2-苯基-嘧啶-4-羧酸甲酯 在 TEA 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以8%的产率得到N-(cyclohexylmethyl)-5,6-dihydroxy-2-phenylpyrimidine-4-carboxamide
  参考文献：
  名称：

  5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein

  摘要：

  The HIV-1 nucleocapsid (NC) protein is a small basic DNA and RNA binding protein that is absolutely necessary for viral replication and thus represents a target of great interest to develop new anti-HIV agents. Moreover, the highly conserved sequence offers the opportunity to escape the drug resistance (DR) that emerged following the highly active antiretroviral therapy (HAART) treatment. On the basis of our previous research, nordihydroguaiaretic acid 1 acts as a NC inhibitor showing moderate antiviral activity and suboptimal drug-like properties due to the presence of the catechol moieties. A bioisosteric catechol replacement approach led us to identify the S-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. Hit validation efforts led to the identification of optimized analogs, as represented by compound 28, showing improved NC inhibition and antiviral activity as well as good ADME and PK properties.

  DOI：

  10.1021/acsmedchemlett.9b00608