methyl 3-[[(1R)-1-(4-fluorophenyl)ethyl]carbamoyl]-5-[methyl(methylsulfonyl)amino]benzoate | 827579-70-4

• 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: methyl 3-[[(1R)-1-(4-fluorophenyl)ethyl]carbamoyl]-5-[methyl(methylsulfonyl)amino]benzoate
• CAS: 827579-70-4
• 化学式: C₁₉H₂₁FN₂O₅S
• 分子量: 408.451
• InChiKey: OEXYCCYXMPICTC-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 3-[[(1R)-1-(4-fluorophenyl)ethyl]carbamoyl]-5-[methyl(methylsulfonyl)amino]benzoate 在 sodium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 1-N-[(2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl]-3-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-(N-methylmethanesulfonamido)benzene-1,3-dicarboxamide
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1)

  摘要：

  We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.

  DOI：

  10.1021/jm049379g
• 作为产物：
  描述：

  5-氨基间苯二甲酸二甲酯 在 吡啶 、 甲醇 、 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 反应 63.0h， 生成 methyl 3-[[(1R)-1-(4-fluorophenyl)ethyl]carbamoyl]-5-[methyl(methylsulfonyl)amino]benzoate
  参考文献：
  名称：

  [EN] 1,3,5-SUBSTITUTED PHENYL DERIVATIVE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
  [FR] DERIVES DE PHENYLE 1,3,5-SUBSTITUES UTILES COMME INHIBITEURS DE LA BETA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER

  摘要：

  本发明涉及1,3,5-苯基取代衍生物化合物，这些化合物是β-分泌酶的抑制剂，可用于治疗β-分泌酶参与的疾病，例如阿尔茨海默病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗β-分泌酶参与疾病中的用途。

  公开号：

  WO2005103020A1

文献信息

• [EN] 1,3,5-SUBSTITUTED PHENYL DERIVATIVE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DERIVES DE PHENYLE 1,3,5-SUBSTITUES UTILES COMME INHIBITEURS DE LA BETA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2005103020A1

  公开（公告）日：2005-11-03

  The present invention is directed to 1,3,5-phenyl substituted derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及1,3,5-苯基取代衍生物化合物，这些化合物是β-分泌酶的抑制剂，可用于治疗β-分泌酶参与的疾病，例如阿尔茨海默病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗β-分泌酶参与疾病中的用途。
• [EN] PYRROLIDIN-3-YL COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] COMPOSES PYRROLIDIN-3-YLE UTILES EN TANT QU'INHIBITEURS DE LA BETA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2006002004A1

  公开（公告）日：2006-01-05

  The present invention is directed to pyrrolidin-3-yl derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及吡咯烷-3-基衍生物化合物，这些化合物是β-分泌酶的抑制剂，并且在治疗涉及β-分泌酶的疾病，如阿尔茨海默病中有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗涉及β-分泌酶的这类疾病中使用这些化合物和组合物。
• Phenylamide and pyridylamide beta-secretase inhibitors for the treatment of alzheimer's disease
  申请人：Barrow C. James

  公开号：US20070142634A1

  公开（公告）日：2007-06-21

  The present invention is directed to phenylamide and pyridylamide derivative compounds of which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及苯胺和吡啶胺衍生物化合物，这些化合物是β-分泌酶的抑制剂，并且在治疗涉及β-分泌酶的疾病，如阿尔茨海默病中有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗涉及β-分泌酶的这类疾病中使用这些化合物和组合物。
• COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Fuchs Klaus

  公开号：US20100144681A1

  公开（公告）日：2010-06-10

  The invention relates to substituted 1,2-ethylenediamines of general formula (I), wherein the radicals R 1 -R 13 , A, B, L and i are as defined in the description and the claims. The invention also relates to the use thereof for treating Alzheimer's disease (AD) and similar diseases.

  该发明涉及一般式(I)的取代1,2-乙二胺化合物，其中基团R1-R13、A、B、L和i如描述和权利要求中所定义。该发明还涉及将其用于治疗阿尔茨海默病（AD）和类似疾病。
• Discovery of Oxadiazoyl Tertiary Carbinamine Inhibitors of β-Secretase (BACE-1)
  作者：Hemaka A. Rajapakse、Philippe G. Nantermet、Harold G. Selnick、Sanjeev Munshi、Georgia B. McGaughey、Stacey R. Lindsley、Mary Beth Young、Ming-Tain Lai、Amy S. Espeseth、Xiao-Ping Shi、Dennis Colussi、Beth Pietrak、Ming-Chih Crouthamel、Katherine Tugusheva、Qian Huang、Min Xu、Adam J. Simon、Lawrence Kuo、Daria J. Hazuda、Samuel Graham、Joseph P. Vacca

  DOI：10.1021/jm061046r

  日期：2006.12.1

  We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere

  我们描述了酶β-分泌酶（BACE-1）的叔卡宾胺衍生抑制剂的发现和优化。这些新的非过渡态衍生的配体结合了一个伯胺与目标酶的催化天冬氨酸相互作用。该系列的优化为抑制剂提供了与进化的过渡态等位基因衍生的BACE-1抑制剂相当的内在和功能性抑制剂。