(1,5-naphthyridin-4-yl)methanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (1,5-naphthyridin-4-yl)methanol
• 英文别名: (1,5-Naphthyridin-4-yl)methanol；1,5-naphthyridin-4-ylmethanol
• 化学式: C₉H₈N₂O
• 分子量: 160.175
• InChiKey: BMPCKYJVDORTKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1,5-naphthyridin-4-yl)methanol 在 氯化亚砜 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 生成 5-((1,5-naphthyridin-4-yl)methoxy)-2-methoxyisonicotinaldehyde
  参考文献：
  名称：

  Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin

  摘要：

  We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of similar to 150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 (36) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).

  DOI：

  10.1021/acsmedchemlett.6b00491