3-hydroxy-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one | 3303-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 3-hydroxy-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 3-hydroxy-2-methyl-3H-pyrido[3,2-d]pyrimidin-4-one；3-Hydroxy-2-methyl-pyrido<3,2-d>pyrimidin-4(3H)-on；Pyrido[3,2-d]pyrimidin-4(3H)-one, 3-hydroxy-2-methyl-；3-hydroxy-2-methylpyrido[3,2-d]pyrimidin-4-one
• CAS: 3303-23-9
• 化学式: C₈H₇N₃O₂
• 分子量: 177.162
• InChiKey: GWWRXYYWBYRCLI-UHFFFAOYSA-N

物化性质

• 沸点：
  404.4±37.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基吡啶-2-羧酸甲酯 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.25h， 生成 3-hydroxy-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Structure–Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease

  摘要：

  Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PA(N) endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PA(N) endonuclease, a class of highly active and selective fragments was developed that displays IC50 values <50 nM. This SAR led to structurally distinct molecules that also displayed IC50 values of similar to 10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.

  DOI：

  10.1021/acs.jmedchem.8b01363

文献信息

• Structure–Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease
  作者：Cy V. Credille、Benjamin L. Dick、Christine N. Morrison、Ryjul W. Stokes、Rebecca N. Adamek、Nicholas C. Wu、Ian A. Wilson、Seth M. Cohen

  DOI：10.1021/acs.jmedchem.8b01363

  日期：2018.11.21

  Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PA(N) endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PA(N) endonuclease, a class of highly active and selective fragments was developed that displays IC50 values <50 nM. This SAR led to structurally distinct molecules that also displayed IC50 values of similar to 10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.