(S)-4-(difluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine | 1432511-64-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-4-(difluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine
• 英文别名: (4S)-4-(difluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-1,3-oxazin-2-amine
• CAS: 1432511-64-2
• 化学式: C₁₁H₁₀F₃N₃O₃
• 分子量: 289.214
• InChiKey: SDFIUMCAVLIIRX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-4-(difluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 以96%的产率得到(S)-4-(5-amino-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine
  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：

  1-(5-bromo-2-fluorophenyl)-2,2-difluoroethanone 在 盐酸 、 titanium(IV) tetraethanolate 、 锂硼氢 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 sodium acetate 、 三氟乙酸 、 copper(l) chloride 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 异丙醇 为溶剂， 反应 1.0h， 生成 (S)-4-(difluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine
  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

文献信息

• β-Secretase (BACE1) Inhibitors with High in Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer’s Disease
  作者：Hans Hilpert、Wolfgang Guba、Thomas J. Woltering、Wolfgang Wostl、Emmanuel Pinard、Harald Mauser、Alexander V. Mayweg、Mark Rogers-Evans、Roland Humm、Daniela Krummenacher、Thorsten Muser、Christian Schnider、Helmut Jacobsen、Laurence Ozmen、Alessandra Bergadano、David W. Banner、Remo Hochstrasser、Andreas Kuglstatter、Pascale David-Pierson、Holger Fischer、Alessandra Polara、Robert Narquizian

  DOI：10.1021/jm400225m

  日期：2013.5.23

  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.