N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide

• 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: N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide
• 英文别名: N-[3-[(2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-4H-pyridin-2-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide
• 化学式: C₂₁H₁₉F₄N₅O
• 分子量: 433.4
• InChiKey: YQEYIBBJTJIMBM-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氰基-3-甲基吡啶甲酸 、 O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 (3S,6R)-6-(5-amino-2-fluorophenyl)-3,5,5-trifluoro-3,6-dimethyl-3,4,5,6-tetrahydropyridin-2-amine 在 水 、 乙酸乙酯 、 magnesium sulfate 、 crude material 、 sodium hydrogen carbonate water 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 1.08h， 以to give N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide (153 mg, 26% yield)的产率得到N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide
  参考文献：
  名称：

  2-amino 3,5,5-trifluoro-3,4,5,6-tetrahydropyridines as BACE1 inhibitors for treatment of Alzheimer's disease

  摘要：

  本发明涉及一种新型BACE1酶抑制剂。该发明的不同方面涉及包含这些化合物的制药组合物以及利用这些化合物治疗减少Aβ沉积有益的疾病，如阿尔茨海默病。

  公开号：

  US09353084B2

文献信息

• 2-Amino-3,5,5-trifluoro-3,4,5,6-tetrahydropyridines as BACE1 inhibitors for treatment of Alzheimer's disease
  申请人：H. LUNDBECK A/S

  公开号：US20150232449A1

  公开（公告）日：2015-08-20

  The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.

  本发明涉及新型BACE1酶抑制剂。发明的不同方面涉及包含所述化合物的药物组合物，以及利用这些化合物治疗减少Aβ沉积有益的疾病，如阿尔茨海默病。
• [EN] COMBINATION TREATMENT COMPRISING ADMINISTRATION OF 2-AMINO-3,5,5-TRIFLUORO-3,4,5,6-TETRAHYDROPYRIDINES<br/>[FR] TRAITEMENT COMBINÉ COMPRENANT L'ADMINISTRATION DE 2-AMINO-3,5,5-TRIFLUORO-3,4,5,6-TÉTRAHYDROPYRIDINES
  申请人：H LUNDBECK AS

  公开号：WO2017025532A1

  公开（公告）日：2017-02-16

  The present invention is directed to the combined use of BACE1 inhibitor of Formula (I) and a compound useful in active or passive Tau immunotherapy, a compound useful in active or passive Aβ peptide immunotherapy, an NMDA receptor antagonists, an acetylcholine esterase inhibitor, an antiepileptic, an anti-inflammatory drug, a Tau aggregation inhibitor or an SSRI for the treatment of neurodegenerative or cognitive disorders.

  本发明涉及利用化合物(I)的BACE1抑制剂与在主动或被动Tau免疫疗法中有用的化合物、在主动或被动Aβ肽免疫疗法中有用的化合物、NMDA受体拮抗剂、乙酰胆碱酯酶抑制剂、抗癫痫药物、抗炎药物、Tau聚集抑制剂或SSRI的联合使用，用于治疗神经退行性或认知障碍。
• Combination treatment comprising administration of 2-amino-3,5,5-trifluoro-3,4,5,6-tetrahydropyridines
  申请人：H. Lundbeck A/S

  公开号：US10004738B2

  公开（公告）日：2018-06-26

  The present invention is directed to the combined use of BACE1 inhibitor of Formula I and a compound useful in active or passive Tau immunotherapy, a compound useful in active or passive Aβ peptide immunotherapy, an NMDA receptor antagonists, an acetylcholine esterase inhibitor, an antiepileptic, an anti-inflammatory drug, a Tau aggregation inhibitor or an SSRI for the treatment of neurodegenerative or cognitive disorders.

  本发明涉及联合使用式 I 的 BACE1 抑制剂 和一种可用于主动或被动 Tau 免疫疗法的化合物、一种可用于主动或被动 Aβ 肽免疫疗法的化合物、一种 NMDA 受体拮抗剂、一种乙酰胆碱酯酶抑制剂、一种抗癫痫药、一种抗炎药、一种 Tau 聚集抑制剂或一种 SSRI 用于治疗神经退行性疾病或认知障碍。
• 2-AMINO-3, 5, 5-TRIFLUORO-3, 4, 5, 6-TETRAHYDROPYRIDINES AS BACE1 INHIBITORS FOR TREATMENT OF ALZHEIMER'S DISEASE
  申请人：H. Lundbeck A/S

  公开号：EP3107897A1

  公开（公告）日：2016-12-28
• Combination Treatment Comprising Administration of 2-Amino-3,5,5-trifluoro-3,4,5,6-tetrahydropyridines
  申请人：H. Lundbeck A/S

  公开号：US20170042895A1

  公开（公告）日：2017-02-16

  The present invention is directed to the combined use of BACE1 inhibitor of Formula I and a compound useful in active or passive Tau immunotherapy, a compound useful in active or passive Aβ peptide immunotherapy, an NMDA receptor antagonists, an acetylcholine esterase inhibitor, an antiepileptic, an anti-inflammatory drug, a Tau aggregation inhibitor or an SSRI for the treatment of neurodegenerative or cognitive disorders.