rac-[1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-carbamic acid tert-butyl ester | 1313525-80-2

• 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: rac-[1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-carbamic acid tert-butyl ester
• 英文别名: (R)-tert-butyl (2-(5-bromo-2-fluorophenyl)-1-hydroxypropan-2-yl)carbamate；rac-[1-(5-bromo-2-fluorophenyl)-2-hydroxy-1-methylethyl]carbamic acid tert-butyl ester；[1-(5-bromo-2-fluorophenyl)-2-hydroxy-1-methylethyl]carbamic acid tert-butyl ester；Tert-butyl [1-(5-bromo-2-fluorophenyl)-2-hydroxy-1-methylethyl]carbamate；tert-butyl N-[2-(5-bromo-2-fluorophenyl)-1-hydroxypropan-2-yl]carbamate
• CAS: 1313525-80-2
• 化学式: C₁₄H₁₉BrFNO₃
• 分子量: 348.212
• InChiKey: QHYACLKGTSIFSS-UHFFFAOYSA-N

物化性质

• 沸点：
  429.8±45.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  rac-[1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-carbamic acid tert-butyl ester 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以83%的产率得到rac-[1-(5-bromo-2-fluoro-phenyl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  合理设计和合成氨基哌嗪酮类β-分泌酶（BACE）抑制剂

  摘要：

  通过合理设计鉴定了BACE的氨基哌嗪酮抑制剂。基于结构的设计指导思想优先级排序和初始外消旋命中数18a显示出良好的活动性。修饰修饰和手性分离产生了40 nM抑制剂（-）-37，它在体内显示淀粉样β肽减少。18a的晶体结构显示出一种结合模式，该结合模式是由与催化天冬氨酸二联体相互作用以及联芳基酰胺修饰物朝S1和S3口袋分布而驱动的。

  DOI：

  10.1016/j.bmcl.2011.10.050
• 作为产物：
  描述：

  (RS)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionic acid methylester 在 sodium tetrahydroborate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 18.0h， 生成 rac-[1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  合理设计和合成氨基哌嗪酮类β-分泌酶（BACE）抑制剂

  摘要：

  通过合理设计鉴定了BACE的氨基哌嗪酮抑制剂。基于结构的设计指导思想优先级排序和初始外消旋命中数18a显示出良好的活动性。修饰修饰和手性分离产生了40 nM抑制剂（-）-37，它在体内显示淀粉样β肽减少。18a的晶体结构显示出一种结合模式，该结合模式是由与催化天冬氨酸二联体相互作用以及联芳基酰胺修饰物朝S1和S3口袋分布而驱动的。

  DOI：

  10.1016/j.bmcl.2011.10.050

文献信息

• AMINO-DIHYDROTHIAZINE AND AMINO-DIOXIDO DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE ANTAGONISTS AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：US20140107109A1

  公开（公告）日：2014-04-17

  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, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

  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在此独立地被定义。该发明还提供了包含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的化合物及其亚式化合物，中间体和用于制备化学式I-II化合物的有用过程和方法。
• [EN] 3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL FOR THE TREATEMENT OF ALZHEIMER'S DISEASE AND OTHER FORMS OF DEMENTIA<br/>[FR] DÉRIVÉS DE 3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE UTILES POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER ET D'AUTRES FORMES DE DÉMENCE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012000933A1

  公开（公告）日：2012-01-05

  The present invention relates to novel 3-amino-5,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta- amyloid.

  本发明涉及作为β-分泌酶抑制剂的新型3-氨基-5,6-二氢-1H-吡嗪-2-酮衍生物，β-分泌酶也称为β-位点淀粉样蛋白裂解酶、BACE、BACE1、Asp2或memapsin2。该发明还涉及包含这些化合物的药物组合物，用于制备这些化合物和组合物的方法，以及用于预防和治疗涉及β-分泌酶的疾病的这些化合物和组合物的用途，如阿尔茨海默病（AD）、轻度认知障碍、老年痴呆、带有Lewy小体的痴呆、唐氏综合征、与中风相关的痴呆、与帕金森病相关的痴呆或与β-淀粉样蛋白相关的痴呆。
• 3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND OTHER FORMS OF DEMENTIA
  申请人：Delgado-Jiménez Francisca

  公开号：US20130102618A1

  公开（公告）日：2013-04-25

  The present invention relates to novel 3-amino-5,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.

  本发明涉及新型3-氨基-5,6-二氢-1H-吡嗪-2-酮衍生物，作为β-分泌酶抑制剂，也被称为β-位点淀粉样蛋白裂解酶、BACE、BACE1、Asp2或memapsin2。该发明还涉及包含这种化合物的药物组合物，用于制备这种化合物和组合物的方法，以及用于预防和治疗涉及β-分泌酶的疾病的这种化合物和组合物的用途，如阿尔茨海默病（AD）、轻度认知障碍、老年痴呆、带有Lewy小体的痴呆、唐氏综合征、与中风相关的痴呆、与帕金森病相关的痴呆或与β-淀粉样蛋白相关的痴呆。
• [EN] 5,6-DIHYDRO-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)<br/>[FR] DÉRIVÉS 5,6-DIHYDRO-IMIDAZO[1,2-A]PYRAZIN-8-YLAMINE UTILES EN TANT QU'INHIBITEURS DE BÊTA SECRÉTASE (BACE)
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012085038A1

  公开（公告）日：2012-06-28

  The present invention relates to novel 5,6-dihydro-imidazo[1,2-a]pyrazin-8- ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebrovascular amyloid angiopathy, multi- infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.

  本发明涉及作为β-分泌酶抑制剂的新型5,6-二氢咪唑[1,2-a]吡嗪-8-胺衍生物，也称为β-位点淀粉样蛋白裂解酶、BACE、BACE1、Asp2或memapsin2。该发明还涉及包含这些化合物的药物组合物，用于制备这些化合物和组合物的方法，以及将这些化合物和组合物用于预防和治疗涉及β-分泌酶的疾病，如阿尔茨海默病（AD）、轻度认知障碍、老年痴呆、带有Lewy小体的痴呆、脑血管淀粉样血管病、多梗死性痴呆、唐氏综合征、与中风相关的痴呆、与帕金森病相关的痴呆或与β-淀粉样蛋白相关的痴呆。
• [EN] PYRAZINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF NEUROLOGICAL DISORDERS<br/>[FR] DERIVES DE PYRAZINE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：NOVARTIS AG

  公开号：WO2011080176A1

  公开（公告）日：2011-07-07

  The invention relates to novel heterocyclic compounds of the formula (I) in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their medical use and to medicaments comprising them.

  该发明涉及公式（I）中的新异环化合物，其中所有变量均如规范中定义，以自由形式或盐形式存在，涉及其制备、医疗用途以及包含它们的药物。