H-(α-CF2H)Phe-OMe | 167612-40-0

• 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: H-(α-CF2H)Phe-OMe
• 英文别名: methyl 2-amino-2-benzyl-3,3-difluoropropanoate
• CAS: 167612-40-0
• 化学式: C₁₁H₁₃F₂NO₂
• 分子量: 229.227
• InChiKey: IZNFZYPWMXVYRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  H-(α-CF2H)Phe-OMe 在 三溴化硼 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 一水合肼 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 10.5h， 生成
  参考文献：
  名称：

  Incorporation of the Unusual C^α-Fluoroalkylamino Acids into Cyclopeptides:  Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior

  摘要：

  A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C-alpha-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-a-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alpha TfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains.

  DOI：

  10.1021/jm0511334
• 作为产物：
  描述：

  L-苯丙氨酸甲酯 在 盐酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 H-(α-CF2H)Phe-OMe
  参考文献：
  名称：

  Incorporation of the Unusual C^α-Fluoroalkylamino Acids into Cyclopeptides:  Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior

  摘要：

  A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C-alpha-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-a-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alpha TfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains.

  DOI：

  10.1021/jm0511334

文献信息

• Peptide Synthesis with α-(Difluoromethyl)-Substituted α-Amino Acids
  作者：Thomas Michel、Beate Koksch、Sergei N. Osipov、Alexander S. Golubev、Joachim Sieler、Klaus Burger

  DOI：10.1135/cccc20021533

  日期：——

  Methodology for the incorporation of α-(difluoromethyl)-substituted α-amino acids into N- and C-terminal positions of dipeptides as well as into position 2 of tri- and tetrapeptides is described.

  将α-(二氟甲基)-取代的α-氨基酸并入二肽的N-和C-末端位置，以及并入三肽和四肽的位置2的方法被描述。
• [EN] BENZYLETHER AND BENZYLAMINO BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] INHIBITEURS DE BENZYLETHER ET BENZYLAMINO DE BETA-SECRETASE POUR TRAITER LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2005051914A1

  公开（公告）日：2005-06-09

  The present invention is directed to benzylether and benzylamino 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.

  本发明涉及苯乙醚和苄胺衍生物化合物，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。
• Amine-based and amide-based inhibitors of semicarbazide-sensitive amine oxidase (SSAO)enzyme activity and VAP-1 mediated adhesion useful for treatment of diseases
  申请人：Salter-Cid M. Luisa

  公开号：US20070078157A1

  公开（公告）日：2007-04-05

  Compositions and methods are disclosed for inhibiting semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1). The compounds disclosed are amine-containing and amide-containing compounds. The compounds and compositions are useful for treatment of diseases, including inflammation, inflammatory diseases and autoimmune disorders.

  本发明公开了抑制半卡巴肼敏感性胺氧化酶（SSAO），也称为血管黏附蛋白-1（VAP-1）的组合物和方法。所公开的化合物是含有胺基和酰胺基的化合物。这些化合物和组合物可用于治疗炎症、炎症性疾病和自身免疫性疾病等疾病。
• Benzylether and benzylamino beta-secretase inhibitors for the treatment of alzheimer's disease
  申请人：Nantermet G. Philippe

  公开号：US20070088165A1

  公开（公告）日：2007-04-19

  The present invention is directed to benzylether and benzylamino derivative compounds of formula (I) 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.

  本发明涉及式(I)的苯甲醚和苯甲氨基衍生物化合物，它们是β-分泌酶酶的抑制剂，并且在治疗β-分泌酶酶涉及的疾病，例如阿尔茨海默病中有用。本发明还涉及包含这些化合物的制药组合物以及在治疗β-分泌酶酶涉及的疾病中使用这些化合物和组合物的用途。
• Benzylether and benzylamino beta-secretase inhibitors for the treatment of Alzheimer's disease
  申请人：Merck & Co., Inc.

  公开号：US07354942B2

  公开（公告）日：2008-04-08

  The present invention is directed to benzylether and benzylamino derivative compounds of formula (I) 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.

  本发明涉及式（I）的苄醚和苄氨基衍生物化合物，它们是β-分泌酶酶的抑制剂，可用于治疗β-分泌酶酶参与的疾病，如阿尔茨海默病。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物和组合物治疗β-分泌酶酶参与的疾病的方法。