(4aR,10aR)-1-propyl-1,2,3,4,4a,5,8,9,10,10a-decahydrobenzo[q]quinolin-6(7H)-one | 367966-55-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4aR,10aR)-1-propyl-1,2,3,4,4a,5,8,9,10,10a-decahydrobenzo[q]quinolin-6(7H)-one
• 英文别名: (4aR,10aR)-1-propyl-1,2,3,4,4a,5,8,9,10,10a-decahydrobenzo[g]quinolin-6(7H)-one；(4aR,10aR)-2,3,4,4a,5,7,8,9,10,10a-Decahydro-1-propylbenzo[g]quinolin-6(1H)-one；(4aR,10aR)-1-propyl-2,3,4,4a,5,7,8,9,10,10a-decahydrobenzo[g]quinolin-6-one
• CAS: 367966-55-0
• 化学式: C₁₆H₂₅NO
• 分子量: 247.381
• InChiKey: QLIKRYHBUISCTR-UKRRQHHQSA-N

物化性质

• 沸点：
  385.0±41.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4aR,10aR)-1-propyl-1,2,3,4,4a,5,8,9,10,10a-decahydrobenzo[q]quinolin-6(7H)-one 在 cerium(III) chloride heptahydrate 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 (4aR,10aR)-1-propyl-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrobenzo[g]quinolin-6-ol
  参考文献：
  名称：

  [EN] NOVEL 1,2,3,4,4a,5,6,7,8,9,10,10a-DODECAHYDROBENZO[G]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF
  [FR] NOUVEAUX COMPOSÉS DE 1,2,3,4,4A,5,6,7,8,9,10,10A-DODÉCAHYDROBENZO[G]QUINOLIN-6-OL ET LEURS UTILISATIONS

  摘要：

  There is disclosed a compound of Formula (II), a method of manufacturing thereof as well as uses thereof.

  公开号：

  WO2023208865A1
• 作为产物：
  描述：

  (E)-ethyl 4-(trans-1-propyloctahydroquinolin-7(1H)-ylidene)butanoate 在 Eaton’s reagent 作用下， 以0.35 g的产率得到(4aR,10aR)-1-propyl-1,2,3,4,4a,5,8,9,10,10a-decahydrobenzo[q]quinolin-6(7H)-one
  参考文献：
  名称：

  [EN] NOVEL 1,2,3,4,4a,5,6,7,8,9,10,10a-DODECAHYDROBENZO[G]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF
  [FR] NOUVEAUX COMPOSÉS DE 1,2,3,4,4A,5,6,7,8,9,10,10A-DODÉCAHYDROBENZO[G]QUINOLIN-6-OL ET LEURS UTILISATIONS

  摘要：

  There is disclosed a compound of Formula (II), a method of manufacturing thereof as well as uses thereof.

  公开号：

  WO2023208865A1

文献信息

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

  公开号：WO2019101917A1

  公开（公告）日：2019-05-31

  The present invention provides compounds of formula (I) 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. Accordingly, the present invention relates to compounds of formula (Id) wherein R1 is H and R2 is selected from one of the substituents (i) and (ii) below; or R1 is selected from one of the substituents (i) and (ii) below and R2 is H; or R1 and R2 are both represented by substituent (i) below; or R1 and R2 are both represented by substituent (ii) below; or R1 is substituent (i) and R2 is substituent (ii); or R1 is substituent (ii) and R2 is substituent (i); (i) (ii) wherein * indicates the attachment point; and wherein the carbon atom at the attachment point on substituent (i) is in the S-configuration; or a pharmaceutically acceptable salt thereof.

  本发明提供了化合物(I)的中间体，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。因此，本发明涉及化合物(I d)的公式，其中R1为H，R2从下面的取代基(i)和(ii)中选择一个；或R1从下面的取代基(i)和(ii)中选择一个，R2为H；或R1和R2都由下面的取代基(i)表示；或R1和R2都由下面的取代基(ii)表示；或R1为取代基(i)，R2为取代基(ii)；或R1为取代基(ii)，R2为取代基(i)；(i) (ii) 其中*表示连接点；取代基(i)上连接点的碳原子处于S构型；或其药用可接受盐。
• [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] A PROCESS FOR THE MANUFACTURING OF (6AR,10AR)-7-PROPYL-6,6A,7,8,9,10,10A,11-OCTAHYDRO-[1,3]DIOXOLO[4',5':5,6]BENZO[1,2-G]QUINOLINE AND (4AR,10AR)-1-PROPYL-1,2,3,4,4A,5,10,10A-OCTAHYDRO-BENZO[G]QUINOLINE-6,7-DIOL<br/>[FR] PROCÉDÉ DE FABRICATION DE (6AR, 10AR)-7-PROPYL -6,6A,7,8,9,10,10 A, 11-OCTAHYDRO-[1,3] DIOXOLO [4',5':5,6] BENZO[1,2-G]QUINOLÉINE ET (4AR,10AR)-1-PROPYL-1,2,3,4,4 A,5,10,10A-OCTAHYDRO-BENZO[G] QUINOLÉINE-6,7-DIOL
  申请人：H LUNDBECK AS

  公开号：WO2020234273A1

  公开（公告）日：2020-11-26

  The present invention relates to a new process for manufacturing (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4',5':5,6]benzo[1,2-g]quinoline with formula (Ib), (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol with formula (I) and salts thereof. Both compounds are for use in the treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediate compounds of said process.

  本发明涉及一种用于制造(6aR,10aR)-7-丙基-6,6a,7,8,9,10,10a,11-八氢-[1,3]二氧杂环[4',5':5,6]苯并[1,2-g]喹啉，化学式为(Ib)，以及(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-八氢-苯并[g]喹啉-6,7-二酚，化学式为(I)及其盐的新工艺。这两种化合物用于治疗神经退行性疾病和疾病，如帕金森病。该发明还涉及所述工艺的新中间体化合物。
• [EN] NEW CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASES<br/>[FR] NOUVEAUX PROMÉDICAMENTS DE CATÉCHOLAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES DE PARKINSON
  申请人：H LUNDBECK AS

  公开号：WO2020234275A1

  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（Id）的公式，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。