5-amino-2-(quinolin-5-yl)oxazole-4-carbonitrile | 1609377-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-amino-2-(quinolin-5-yl)oxazole-4-carbonitrile
• CAS: 1609377-42-5
• 化学式: C₁₃H₈N₄O
• 分子量: 236.233
• InChiKey: JMSMOFZIMWHLCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.73
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 5-amino-2-(quinolin-5-yl)oxazole-4-carbonitrile 、 三氟乙酸 在 sodium methylate 、 sodium tetrahydroborate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 2.0h， 生成 5-(methylamino)-2-(quinolin-5-yl)oxazole-4-carbonitrile trifluoroacetate
  参考文献：
  名称：

  Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase as Anti-Stroke Therapies

  摘要：

  A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.

  DOI：

  10.1021/jm401915r
• 作为产物：
  描述：

  喹啉-5-羧酸 、 对苯二磺酸氨基丙二酰丁氰 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 生成 5-amino-2-(quinolin-5-yl)oxazole-4-carbonitrile
  参考文献：
  名称：

  Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase as Anti-Stroke Therapies

  摘要：

  A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.

  DOI：

  10.1021/jm401915r