methyl 5-(prop-2-ynyloxy)pyrazine-2-carboxylate | 1432511-53-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: methyl 5-(prop-2-ynyloxy)pyrazine-2-carboxylate
• 英文别名: Methyl 5-prop-2-ynoxypyrazine-2-carboxylate；methyl 5-prop-2-ynoxypyrazine-2-carboxylate
• CAS: 1432511-53-9
• 化学式: C₉H₈N₂O₃
• 分子量: 192.174
• InChiKey: RLNRAHFLIVPWPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-(prop-2-ynyloxy)pyrazine-2-carboxylate 在 锂硼氢 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以81.5%的产率得到5-(prop-2-yn-1-yloxy)pyrazine-2-carboxylic acid
  参考文献：
  名称：

  β-Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease

  摘要：

  An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pK(a) and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF A beta 40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of A beta 40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.

  DOI：

  10.1021/jm400225m
• 作为产物：
  描述：

  2-丙炔-1-醇 、 5-氯吡嗪-2-羧酸甲酯 在 potassium tert-butylate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以32%的产率得到methyl 5-(prop-2-ynyloxy)pyrazine-2-carboxylate
  参考文献：
  名称：

  β-Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease

  摘要：

  An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pK(a) and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF A beta 40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of A beta 40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.

  DOI：

  10.1021/jm400225m