ethyl 5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylate | 1432511-65-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: ethyl 5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylate
• 英文别名: Ethyl 5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylate；ethyl 5-(trifluoromethyl)-4,5-dihydro-1,2-oxazole-3-carboxylate
• CAS: 1432511-65-3
• 化学式: C₇H₈F₃NO₃
• 分子量: 211.141
• InChiKey: BNEMJEWGMLPQCF-UHFFFAOYSA-N

物化性质

• 沸点：
  188.6±43.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylate 在 sodium tetrahydroborate 、 正丁基锂 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 甲酸铵 、 三乙胺 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 65.5h， 生成 (4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-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：

  ethyl chlorooximidoacetate 、 3,3,3-三氟丙烯 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 反应 60.0h， 以3.2 g的产率得到ethyl 5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylate
  参考文献：
  名称：

  [EN] FLUOROMETHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES
  [FR] FLUOROMÉTHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES

  摘要：

  本发明提供了具有BACE1抑制活性的化合物(I)的公式，它们的制备，包含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/或预防治疗例如阿尔茨海默病等疾病方面是有用的。

  公开号：

  WO2013110622A1

文献信息

• Fluoromethyl-5,6-dihydro-4H-[1,3]OXAZINES
  申请人：F. Hoffmann-La Roche AG

  公开号：US09067926B2

  公开（公告）日：2015-06-30

  Provided herein is a compound of formula I: as wells as a pharmaceutical composition, a process of making and a method of using a compound of formula I. The compounds of formula I are BACE1 inhibitors useful for the treatement of, for example, Alzheimer's Disease.

  本文提供了I式化合物，以及一种制药组合物、制药过程和使用I式化合物的方法。I式化合物是BACE1抑制剂，可用于治疗例如阿尔茨海默病等疾病。
• FLUOROMETHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES
  申请人：F. Hoffmann-La Roche AG

  公开号：US20150031690A1

  公开（公告）日：2015-01-29

  The present invention provides a compound of formula (I) having BACE1 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.

  本发明提供了一种具有BACE1抑制活性的化合物（I）的制备方法，包括含有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在治疗和/或预防例如阿尔茨海默病等疾病方面具有用途。
• US9067926B2
  申请人：——

  公开号：US9067926B2

  公开（公告）日：2015-06-30
• 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.
• [EN] FLUOROMETHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES<br/>[FR] FLUOROMÉTHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013110622A1

  公开（公告）日：2013-08-01

  The present invention provides a compound of formula (I) having BACE1 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.

  本发明提供了具有BACE1抑制活性的化合物(I)的公式，它们的制备，包含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/或预防治疗例如阿尔茨海默病等疾病方面是有用的。