(4R,5R)-5-fluoro-4-(2-fluoro-5-nitrophenyl)-4-(fluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine | 1402413-24-4

• 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: (4R,5R)-5-fluoro-4-(2-fluoro-5-nitrophenyl)-4-(fluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine
• 英文别名: (4S,5R)-5-fluoro-4-fluoromethyl-4-(2-fluoro-5-nitro-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine；(4S,5R)-5-fluoro-4-(fluoromethyl)-4-(2-fluoro-5-nitrophenyl)-5,6-dihydro-1,3-oxazin-2-amine
• CAS: 1402413-24-4
• 化学式: C₁₁H₁₀F₃N₃O₃
• 分子量: 289.214
• InChiKey: BIOZHPLBQDEHRO-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 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：

  (4R,5R)-5-fluoro-4-(2-fluoro-5-nitrophenyl)-4-(fluoromethyl)-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89%的产率得到(4R,5S)-4-(5-amino-2-fluorophenyl)-5-fluoro-4-(fluoromethyl)-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-(2-氟苯基)-2-羟基乙烷酮 在 盐酸 、 titanium(IV) tetraethanolate 、 锂硼氢 、 全氟丁基磺酰氟 、 硫酸 、 硝酸 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 三氟乙酸 、 copper(l) chloride 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 (4R,5R)-5-fluoro-4-(2-fluoro-5-nitrophenyl)-4-(fluoromethyl)-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

• 1,3-OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
  申请人：Hilpert Hans

  公开号：US20120258962A1

  公开（公告）日：2012-10-11

  The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明提供了具有BACE1和/或BACE2抑制活性的式I的4-(3-氨基苯基)-5,6-二氢-4H-[1,3]噁嗪-2-胺，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗阿尔茨海默病和2型糖尿病等疾病方面是有用的。
• 1,3-Oxazines as Bace1 and/or Bace2 Inhibitors
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20140243325A1

  公开（公告）日：2014-08-28

  The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明提供了公式I的4-(3-氨基苯基)-5,6-二氢-4H-[1,3]噁唑-2-胺，具有BACE1和/或BACE2抑制活性，其制备方法，包含它们的制药组合物以及它们作为治疗活性物质的用途。本发明的活性化合物可用于治疗和/或预防阿尔茨海默病和2型糖尿病等疾病。
• 1,3-Oxazines As Bace1 And/Or Bace2 Inhibitors
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150322054A1

  公开（公告）日：2015-11-12

  The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明提供了具有BACE1和/或BACE2抑制活性的4-(3-氨基苯基)-5,6-二氢-4H-[1,3]噁唑-2-胺（式I），它们的制造，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防例如阿尔茨海默病和2型糖尿病方面是有用的。
• US8754075B2
  申请人：——

  公开号：US8754075B2

  公开（公告）日：2014-06-17
• US9115098B2
  申请人：——

  公开号：US9115098B2

  公开（公告）日：2015-08-25