(4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol | 1123299-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol
• 英文别名: (4aR,10aR)-1-propyl-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinoline-6,7-diol
• CAS: 1123299-97-7
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: HZPDHOOVQQYBJP-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol 在 甲酸 、 氯磺酰异氰酸酯 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 以406 mg的产率得到(4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl sulfamate
  参考文献：
  名称：

  [EN] NEW CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE
  [FR] NOUVEAUX PROMÉDICAMENTS DE CATÉCHOLAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE LA MALADIE DE PARKINSON

  摘要：

  The present invention provides sulfamate derivative prodrugs of the dopamine agonist (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol, their use in the treatment of conditions for which treatment with a dopamine agonist is therapeutically beneficial and pharmaceutical compositions comprising compounds of the invention. Compounds according to the invention are of formula (Id), wherein R1 and R2 are each independently selected from H, and substituent (iii) below, wherein * indicates the attachment point to oxygen, wherein R3 is selected from H and COR4, and wherein R4 is selected from H and C1-C6 alkyl, with the proviso that R1 and R2 cannot both be H,15 or a pharmaceutically acceptable salt thereof.

  公开号：

  WO2022106352A1

文献信息

• [EN] CATECHOLAMINE CARBAMATE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON S DISEASE<br/>[FR] PROMÉDICAMENTS DE CARBAMATE DE CATÉCHOLAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE LA MALADIE DE PARKINSON
  申请人：H LUNDBECK AS

  公开号：WO2020234277A1

  公开（公告）日：2020-11-26

  The present invention provides compounds of formula (Id) that are prodrugs of catecholamine for use in treatment of neurodegenerative diseases and disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating neurodegenerative or neuropsychiatric diseases and disorders using the compounds of the invention, in particular Parkinson's disease.

  本发明提供了化合物的公式（Id），这些化合物是儿茶酚胺的前药，用于治疗神经退行性疾病和紊乱。本发明还提供了包括本发明化合物的药物组合物，以及使用本发明化合物治疗神经退行性或神经精神疾病和紊乱的方法，特别是帕金森病。
• CATECHOLAMINE DERIVATIVES AND PRODRUGS THEREOF
  申请人：Jorgensen Morten

  公开号：US20090062324A1

  公开（公告）日：2009-03-05

  The present invention relates to novel catecholamine derivatives of Formula I, to processes for their preparation, pharmaceutical compositions containing them and to their use in therapy.

  本发明涉及公式I的新型儿茶酚胺衍生物，以及其制备方法、含有它们的药物组合物，以及它们在治疗中的应用。
• [EN] NEW CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE<br/>[FR] NOUVEAUX PROMÉDICAMENTS À BASE DE CATÉCHOLAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE LA MALADIE DE PARKINSON
  申请人：H LUNDBECK AS

  公开号：WO2020234274A1

  公开（公告）日：2020-11-26

  The present invention provides compounds of formula (Id) that are prodrugs of catecholamine for use in treatment of neurodegenerative diseases and disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating neurodegenerative or neuropsychiatric diseases and disorders using the compounds of the invention, in particular Parkinson's disease.

  本发明提供了式（Id）的化合物，这些化合物是儿茶酚胺的前药，用于治疗神经退行性疾病和紊乱。本发明还提供了包括本发明化合物的药物组合物，以及使用本发明化合物治疗神经退行性或神经精神疾病和紊乱的方法，特别是帕金森病。
• [EN] A PROCESS FOR THE MANUFACTURE OF (2S,3S,4S,5R,6S)-3,4,5-TRIHYDROXY-6-(((4AR,10AR)-7-HYDROXY-1-PROPYL-1,2,3,4,4A,5,10,10A-OCTAHYDROBENZO[G]QUINOLIN-6-YL)OXY)TETRAHYDRO-2H-PYRAN-2-CARBOXYLIC ACID AND INTERMEDIATE THEREOF<br/>[FR] PROCÉDÉ DE FABRICATION DE (2S,3S,4S,5R,6S) -3,4,5-TRIHYDROXY-6-(((4AR,10AR)-HYDROXY-1-PROPYL-1,2,3,4,4 A,5,10,10A-OCTAHYDROBENZO[G]QUINOLIN-6-YL)OXY)TÉTRAHYDRO-2H-PYRAN-2-CARBOXYLIQUE ET UN INTERMÉDIAIRE DE CELUI-CI
  申请人：H LUNDBECK AS

  公开号：WO2020234270A1

  公开（公告）日：2020-11-26

  The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5- trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a- octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and pharmaceutically acceptable salts thereof. The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to a new intermediate of said process.

  本发明涉及一种制造(2S,3S,4S,5R,6S)-3,4,5-三羟基-6-(((4aR,10aR)-7-羟基-1-丙基-1,2,3,4,4a,5,10,10a-辛氢苯并[g]喹啉-6-基)氧基)四氢-2H-吡喃-2-羧酸（化学式见下文）及其药用盐的过程。化学式（Id）的化合物是一种儿茶酚胺的前药，用于治疗神经退行性疾病和帕金森病等疾病。该发明还涉及该过程的新中间体。
• [EN] ADMINISTRATION OF CATECHOLAMINE PRODRUGS IN COMBINATION WITH A 5-HT2B ANTAGONIST<br/>[FR] ADMINISTRATION DE PROMÉDICAMENTS DE CATÉCHOLAMINE EN COMBINAISON AVEC UN ANTAGONISTE DE 5-HT2B
  申请人：H LUNDBECK AS

  公开号：WO2020070099A1

  公开（公告）日：2020-04-09

  The present invention provides combinations comprising treatment with compounds that are prodrugs of the dopamine agonist (4aR,10aR)-1-n-Propyl-1,2,3,4,4a,5,10,10a- octahydro-benzo[g]quinoline-6,7-diol, in particular compounds of formula (Ia) below or a pharmaceutically acceptable salt thereof, together with a 5-HT2B antagonist. R1 and R2 are selected independently from the group consisting of H, C1-6 alkyl and saturated monocyclic C3-6 cycloalkyl, or one of R1 and R2 is H and the other is phenyl, or R1 and R2 are connected to form a saturated monocyclic 3-6 cycloalkyl.Especially, the invention is directed to the combined use of said compounds in the treatment of Parkinson's disease and/or other conditions for which treatment with a dopamine agonist is therapeutically beneficial. The present invention also provides pharmaceutical compositions comprising said compounds and a 5-HT2B antagonist. In a separate aspect, the invention relates to new compounds that are prodrugs of (4aR,10aR)-1-n-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol wherein R1 and R2 are individually selected from the group consisting of H, C1-6 alkyl and saturated monocyclic C3-6 cycloalkyl; or a pharmaceutically acceptable salt thereof; with the proviso that both R1 and R2 cannot be H at the same time.

  本发明提供了包括与多巴胺激动剂(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-辛氢-苯并[g]喹啉-6,7-二酚的前药一起治疗的组合物，特别是下面的式(Ia)化合物或其药学上可接受的盐，以及5-HT2B拮抗剂。R1和R2分别从H、C1-6烷基和饱和单环C3-6环烷基组成的群体中选择，或者R1和R2中的一个是H，另一个是苯基，或者R1和R2连接形成饱和的单环3-6环烷基。特别地，本发明针对上述化合物在帕金森病的治疗中的联合使用以及治疗多巴胺激动剂具有治疗益处的其他疾病。本发明还提供了包括上述化合物和5-HT2B拮抗剂的药物组合物。在另一个方面，本发明涉及新的化合物，这些化合物是(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-辛氢-苯并[g]喹啉-6,7-二酚的前药，其中R1和R2分别从H、C1-6烷基和饱和单环C3-6环烷基组成的群体中选择；或者其药学上可接受的盐；但R1和R2不能同时为H。