(5R)-5-(5-bromo-2-fluorophenyl)-5-methylmorpholine-3-thione | 1392104-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (5R)-5-(5-bromo-2-fluorophenyl)-5-methylmorpholine-3-thione
• 英文别名: (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione
• CAS: 1392104-98-1
• 化学式: C₁₁H₁₁BrFNOS
• 分子量: 304.183
• InChiKey: BBEGEURGYFVXPR-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 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：
  53.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5R)-5-(5-bromo-2-fluorophenyl)-5-methylmorpholine-3-thione 在 叔丁基过氧化氢 、 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 21.0h， 生成 (5R)-5-(5-Bromo-2-fluorophenyl)-5-methyl-5,6-dihydro-2H-1,4-oxazin-3-amine
  参考文献：
  名称：

  1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS

  摘要：

  本发明提供了具有BACE1和/或BACE2抑制活性的式I的1,4噁嗪，以及它们的制备方法、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型糖尿病等疾病中是有用的。

  公开号：

  US20120196863A1
• 作为产物：
  描述：

  (RS)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionic acid methylester 在 lithium aluminium tetrahydride 、 tetraphosphorus decasulfide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.83h， 生成 (5R)-5-(5-bromo-2-fluorophenyl)-5-methylmorpholine-3-thione
  参考文献：
  名称：

  1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads

  摘要：

  1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pK(a) while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprotein efflux. This led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF A beta levels, respectively, in mouse and dog models. The amyloid lowering potential of these molecules makes them valuable leads in the search for new BACE1 inhibitors for the treatment of Alzheimer's disease.

  DOI：

  10.1021/acs.jmedchem.5b01101

文献信息

• 1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS
  申请人：Andreini Matteo

  公开号：US20120196863A1

  公开（公告）日：2012-08-02

  The present invention provides 1,4 Oxazines 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1,4噁嗪，以及它们的制备方法、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型糖尿病等疾病中是有用的。
• 1,4 oxazines as BACE1 and/or BACE2 inhibitors
  申请人：Andreini Matteo

  公开号：US08399459B2

  公开（公告）日：2013-03-19

  The present invention provides 1,4 Oxazines 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1,4噁唑烷的公式I，它们的制造方法，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/或预防治疗阿尔茨海默病和2型糖尿病等方面具有用途。
• US8399459B2
  申请人：——

  公开号：US8399459B2

  公开（公告）日：2013-03-19
• [EN] 1,4 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS<br/>[FR] 1,4-OXAZINES EN TANT QU'INHIBITEURS DE BACE1 ET/OU BACE2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012104263A2

  公开（公告）日：2012-08-09

  The present invention relates to 1,4 Oxazines 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.
• 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads
  作者：Frederik J. R. Rombouts、Gary Tresadern、Oscar Delgado、Carolina Martínez-Lamenca、Michiel Van Gool、Aránzazu García-Molina、Sergio A. Alonso de Diego、Daniel Oehlrich、Hana Prokopcova、José Manuel Alonso、Nigel Austin、Herman Borghys、Sven Van Brandt、Michel Surkyn、Michel De Cleyn、Ann Vos、Richard Alexander、Gregor Macdonald、Dieder Moechars、Harrie Gijsen、Andrés A. Trabanco

  DOI：10.1021/acs.jmedchem.5b01101

  日期：2015.10.22

  1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pK(a) while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprotein efflux. This led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF A beta levels, respectively, in mouse and dog models. The amyloid lowering potential of these molecules makes them valuable leads in the search for new BACE1 inhibitors for the treatment of Alzheimer's disease.