(S)-4-(2-fluoro-5-nitrophenyl)-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine | 1301740-77-1

• 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-(2-fluoro-5-nitrophenyl)-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine
• 英文别名: (S)-4-(2-fuoro-5-nitrophenyl)-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine；(S)-4-(2-fluoro-5-nitro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine；(4S)-4-(2-fluoro-5-nitrophenyl)-4-methyl-5,6-dihydro-1,3-oxazin-2-amine
• CAS: 1301740-77-1
• 化学式: C₁₁H₁₂FN₃O₃
• 分子量: 253.233
• InChiKey: WCULHMKBLSBJLN-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 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：
  5

反应信息

• 作为反应物：
  描述：

  (S)-4-(2-fluoro-5-nitrophenyl)-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine 在 palladium 10% on activated carbon 、 氢气 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 20.5h， 生成 (S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide
  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：

  N-[[(2S)-2-(2-fluoro-5-nitrophenyl)-4-hydroxybutan-2-yl]carbamothioyl]benzamide 在 硫酸 、 N,N-二异丙基乙胺 、 碘甲烷 作用下， 以 乙腈 为溶剂， 反应 35.5h， 生成 (S)-4-(2-fluoro-5-nitrophenyl)-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine
  参考文献：
  名称：

  AMINOTHIAZINE OR AMINOOXAZINE DERIVATIVE HAVING AMINO LINKER

  摘要：

  本发明提供了一种治疗由淀粉样蛋白β的产生、分泌或沉积引起的疾病的药物，例如以下式(I)的化合物，其中R1、R2a、R2b、R3、R4、R5、X、L1、L2、A、环B和虚线在规范中有定义，其药学上可接受的盐或溶剂化合物。

  公开号：

  US20120238557A1

文献信息

• [EN] AMINO OXAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMINO-OXAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011070029A1

  公开（公告）日：2011-06-16

  This invention relates to 5,6-dihydro-4H-[1,3]oxazin-2-ylamine compounds of the formula (I) wherein R1 to R5 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the treatment or prevention of diseases such as diabetes.

  这项发明涉及式(I)的5,6-二氢-4H-[1,3]噁嗪-2-胺类化合物，其中R1至R5如描述和权利要求中定义的那样，以及其药用盐。这些化合物是BACE2抑制剂，可用作治疗或预防糖尿病等疾病的药物。
• 1,3-OXAZINES AS BACE 1 AND/OR BACE2 INHIBITORS
  申请人：Hilpert Hans

  公开号：US20120295900A1

  公开（公告）日：2012-11-22

  The present invention provides compounds 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.

  本发明提供具有BACE1和/或BACE2抑制活性的化合物，它们的制备方法，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/或预防治疗例如阿尔茨海默病和2型糖尿病方面是有用的。
• AMINO OXAZINE DERIVATIVES
  申请人：Banner David

  公开号：US20110144098A1

  公开（公告）日：2011-06-16

  This invention relates to 5,6-dihydro-4H-[1,3]oxazin-2-ylamine compounds of the formula wherein R 1 to R 5 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the treatment or prevention of diseases such as diabetes.

  这项发明涉及式中R1至R5如描述和索赔中所定义的5,6-二氢-4H-[1,3]噁唑啉-2-胺化合物，以及其药学上可接受的盐。这些化合物是BACE2抑制剂，可用作治疗或预防糖尿病等疾病的药物。
• OXAZINE DERIVATIVES
  申请人：Masui Moriyasu

  公开号：US20120245157A1

  公开（公告）日：2012-09-27

  The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-β proteins. A compound of the formula (I): wherein R 1 , R 2a , R 2b , R 3 , R 4a , R 4b , ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.

  本发明提供了一种如下所述的化合物作为治疗或预防由淀粉样蛋白-β的产生、分泌或沉积引起的疾病的药物。式(I)的化合物：其中R1、R2a、R2b、R3、R4a、R4b、环A和虚线在说明书中有定义，其药用可接受的盐或其溶剂化合物。
• BACE1 inhibitors: A head group scan on a series of amides
  作者：Thomas J. Woltering、Wolfgang Wostl、Hans Hilpert、Mark Rogers-Evans、Emmanuel Pinard、Alexander Mayweg、Martin Göbel、David W. Banner、Jörg Benz、Massimiliano Travagli、Martina Pollastrini、Guido Marconi、Emanuele Gabellieri、Wolfgang Guba、Harald Mauser、Matteo Andreini、Helmut Jacobsen、Eoin Power、Robert Narquizian

  DOI：10.1016/j.bmcl.2013.05.003

  日期：2013.7

  A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment. (C) 2013 Elsevier Ltd. All rights reserved.