5-(amino)-2-(naphthalen-1-yl)oxazole-4-carbonitrile | 1222851-62-8

• 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-1-yl)oxazole-4-carbonitrile
• 英文别名: 5-amino-2-(naphthalen-1-yl)oxazole-4-carbonitrile；5-Amino-2-(1-naphthalenyl)-4-oxazolecarbonitrile；5-amino-2-naphthalen-1-yl-1,3-oxazole-4-carbonitrile
• CAS: 1222851-62-8
• 化学式: C₁₄H₉N₃O
• mdl: MFCD22756419
• 分子量: 235.245
• InChiKey: XXGBLYFVTUUMGE-UHFFFAOYSA-N

物化性质

• 沸点：
  510.5±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(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：

  5-(amino)-2-(naphthalen-1-yl)oxazole-4-carbonitrile 在 亚硝酸特丁酯 、 copper dichloride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.5h， 生成
  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：

  2-氨基丙二腈 、 1-萘甲酸 在 propylphosphonic anhydride 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 生成 5-(amino)-2-(naphthalen-1-yl)oxazole-4-carbonitrile
  参考文献：
  名称：

  [EN] INHIBITORS OF HUMAN 12/15-LIPOXYGENASE
  [FR] INHIBITEURS DE LA 12/15-LIPOXYGÉNASE- HUMAINE

  摘要：

  一项系统性筛选发现了一类化合物，具有对12/15-脂氧合酶的抑制作用。因此，本发明涉及使用这些化合物来抑制12/15-脂氧合酶并治疗涉及12/15-脂氧合酶的疾病。典型的疾病包括但不限于中风、脑室周围白质损伤、心脏骤停复苏、动脉硬化、帕金森病、阿尔茨海默病和乳腺癌。

  公开号：

  WO2015027146A1

文献信息

• INHIBITORS OF HUMAN 12/15-LIPOXYGENASE
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US20160168137A1

  公开（公告）日：2016-06-16

  A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.

  一项系统筛查已经发现了一类化合物，具有对12/15-脂氧化酶抑制作用。因此，本发明涉及使用这些化合物来抑制12/15-脂氧化酶并治疗涉及12/15-脂氧化酶的疾病。示例疾病包括但不限于中风、室旁白质脑病、心脏骤停复苏、动脉粥样硬化、帕金森病、阿尔茨海默病和乳腺癌。
• Inhibitors of human 12/15-lipoxygenase
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US10287279B2

  公开（公告）日：2019-05-14

  A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.

  通过系统筛选，发现了一系列对 12/15 脂氧合酶具有抑制作用的化合物。因此，本发明涉及使用这些化合物来抑制 12/15 脂氧合酶和治疗涉及 12/15 脂氧合酶的病症。示例性病症包括但不限于中风、室周白斑病、心脏骤停复苏、动脉粥样硬化、帕金森病、阿尔茨海默病和乳腺癌。
• 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.
• [EN] INHIBITORS OF HUMAN 12/15-LIPOXYGENASE<br/>[FR] INHIBITEURS DE LA 12/15-LIPOXYGÉNASE- HUMAINE
  申请人：GEN HOSPITAL CORP

  公开号：WO2015027146A1

  公开（公告）日：2015-02-26

  A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.

  一项系统性筛选发现了一类化合物，具有对12/15-脂氧合酶的抑制作用。因此，本发明涉及使用这些化合物来抑制12/15-脂氧合酶并治疗涉及12/15-脂氧合酶的疾病。典型的疾病包括但不限于中风、脑室周围白质损伤、心脏骤停复苏、动脉硬化、帕金森病、阿尔茨海默病和乳腺癌。