methyl 5,6-dihydroxy-2-phenethylpyrimidine-4-carboxylate | 1189791-46-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 5,6-dihydroxy-2-phenethylpyrimidine-4-carboxylate
• 英文别名: methyl 5-hydroxy-6-oxo-2-(2-phenylethyl)-1H-pyrimidine-4-carboxylate
• CAS: 1189791-46-5
• 化学式: C₁₄H₁₄N₂O₄
• 分子量: 274.276
• InChiKey: UHXJCFGQJZYVLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5,6-dihydroxy-2-phenethylpyrimidine-4-carboxylate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以35 mg的产率得到5,6-dihydroxy-2-phenethylpyrimidine-4-carboxylic acid
  参考文献：
  名称：

  RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information

  摘要：

  Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding wits demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.

  DOI：

  10.1021/jm900597q
• 作为产物：
  描述：

  以 间二甲苯 为溶剂， 反应 4.0h， 生成 methyl 5,6-dihydroxy-2-phenethylpyrimidine-4-carboxylate
  参考文献：
  名称：

  RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information

  摘要：

  Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding wits demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.

  DOI：

  10.1021/jm900597q

文献信息

• 5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein
  作者：Savina Malancona、Mattia Mori、Paola Fezzardi、Marisabella Santoriello、Andreina Basta、Martina Nibbio、Lesia Kovalenko、Roberto Speziale、Maria Rosaria Battista、Antonella Cellucci、Nadia Gennari、Edith Monteagudo、Annalise Di Marco、Alessia Giannini、Rajhans Sharma、Manuel Pires、Eleonore Real、Maurizio Zazzi、Maria Chiara Dasso Lang、Davide De Forni、Francesco Saladini、Yves Mely、Vincenzo Summa、Steven Harper、Maurizio Botta

  DOI：10.1021/acsmedchemlett.9b00608

  日期：2020.5.14

  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.