5-Amino-2-naphthalen-2-yl-1,3-oxazole-4-carbonitrile | 1493163-90-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-Amino-2-naphthalen-2-yl-1,3-oxazole-4-carbonitrile
• CAS: 1493163-90-8
• 化学式: C₁₄H₉N₃O
• mdl: MFCD23174774
• 分子量: 235.245
• InChiKey: ZVKHTJDFUGLIOY-UHFFFAOYSA-N

物化性质

• 沸点：
  510.5±60.0 °C(predicted)
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 5-Amino-2-naphthalen-2-yl-1,3-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-(naphthalen-2-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：

  对苯二磺酸氨基丙二酰丁氰 、 2-萘甲酸 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-naphthalen-2-yl-1,3-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

文献信息

• Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase as Anti-Stroke Therapies
  作者：Ganesha Rai、Netra Joshi、Joo Eun Jung、Yu Liu、Lena Schultz、Adam Yasgar、Steve Perry、Giovanni Diaz、Qiangli Zhang、Victor Kenyon、Ajit Jadhav、Anton Simeonov、Eng H. Lo、Klaus van Leyen、David J. Maloney、Theodore R. Holman

  DOI：10.1021/jm401915r

  日期：2014.5.22

  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.