(R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol | 1228571-14-9

• 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: (R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol
• 英文别名: (2R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol
• CAS: 1228571-14-9
• 化学式: C₉H₁₁BrFNO
• 分子量: 248.095
• InChiKey: HGJUZIPMXALMKU-VIFPVBQESA-N

物化性质

• 沸点：
  342.0±37.0 °C(Predicted)
• 密度：
  1.539±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol 在 ammonium hydroxide 、 tetraphosphorus decasulfide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.83h， 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-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
• 作为产物：
  描述：

  (RS)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionic acid methylester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 (R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol
  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

• BRIDGED BICYCLIC AMINO THIAZINE DIOXIDE COMPOUNDS AS INHIBITORS OF BETA-SECRETASE AND METHODS OF USE THEREOF
  申请人：AMGEN INC.

  公开号：US20150038497A1

  公开（公告）日：2015-02-05

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I： 其中化学式I中的变量A4、A5、A6、A8、R1、R2、R3、R7和n，在本文中分别定义。该发明还提供了包括这些化合物的药物组合物，以及这些化合物和组合物用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的对应用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II和其亚式化合物、化学式III的化合物、中间体以及用于制备化学式I-III及其亚式化合物的化合物的制备的过程和方法。
• [EN] 2,5,6,7-TETRAHYDRO-[1,4]OXAZEPIN-3-YLAMINE OR 2,3,6,7-TETRAHYDRO-[1,4]OXAZEPIN-5-YLAMINE COMPOUNDS<br/>[FR] COMPOSÉS DE 2,5,6,7-TÉTRAHYDRO-[1,4]OXAZÉPIN-3-YLAMINE OU DE 2,3,6,7-TÉTRAHYDRO-[1,4]OXAZÉPIN-5-YLAMINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011138293A1

  公开（公告）日：2011-11-10

  This invention relates to compounds of the formula (I), wherein A, B and R1 to R7 are as described below, or to pharmaceutically acceptable salts thereof. These compounds are BACE1 and/or BACE2 inhibitors and can be used as 5 medicaments for the therapeutic and/or prophylactic treatment of diseases such as Alzheimer's disease, diabetes, particularly type 2 diabetes, and other metabolic disorders.

  这项发明涉及式(I)的化合物，其中A、B和R1至R7如下所述，或其药学上可接受的盐。这些化合物是BACE1和/或BACE2抑制剂，可用作治疗和/或预防治疗阿尔茨海默病、糖尿病，特别是2型糖尿病，以及其他代谢紊乱疾病的药物。
• 2,5,6,7-TETRAHYDRO-[1,4]OXAZEPIN-3-YLAMINE OR 2,3,6,7-TETRAHYDRO-[1,4]OXAZEPIN-5-YLAMINE COMPOUNDS
  申请人：Banner David

  公开号：US20110312937A1

  公开（公告）日：2011-12-22

  This invention relates to compounds of the formula wherein A, B and R 1 to R 7 are as described below, or to pharmaceutically acceptable salts thereof. These compounds are BACE1 and/or BACE2 inhibitors and can be used as medicaments for the therapeutic and/or prophylactic treatment of diseases such as Alzheimer's disease, diabetes, particularly type 2 diabetes, and other metabolic disorders.

  这项发明涉及以下式的化合物 其中A、B和R1至R7如下所述，或其药学上可接受的盐。这些化合物是BACE1和/或BACE2抑制剂，可用作治疗和/或预防治疗阿尔茨海默病、糖尿病，特别是2型糖尿病，以及其他代谢紊乱疾病的药物。
• [EN] 5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES<br/>[FR] 5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015091595A1

  公开（公告）日：2015-06-25

  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'的化合物，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/或预防治疗阿尔茨海默病等疾病中是有用的。
• 3-AMINO-5-PHENYL-5,6-DIHYDRO-2H-[1,4]OXAZINES
  申请人：Andreini Matteo

  公开号：US20110046122A1

  公开（公告）日：2011-02-24

  The present invention relates to 3-Amino-5-phenyl-5,6-dihydro-2H-[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.

  本发明涉及具有BACE1和/或BACE2抑制活性的化学式I的3-氨基-5-苯基-5,6-二氢-2H-[1,4]噁嗪，以及它们的制备、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具有用途。