(R)-11-hydroxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yI hydrogen sulfate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (R)-11-hydroxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yI hydrogen sulfate
• 英文别名: (R)-Apomorphine-10-sulfate；[(6aR)-11-hydroxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl] hydrogen sulfate
• 化学式: C₁₇H₁₇NO₅S
• 分子量: 347.392
• InChiKey: IHOVAMLPXSKBSG-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  盐酸去水吗啡 在 三氧化硫吡啶 作用下， 反应 17.0h， 以98.8%的产率得到(R)-11-hydroxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yI hydrogen sulfate
  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：

  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。

  公开号：

  WO2019101917A1

文献信息

• Catecholamine prodrugs for use in the treatment of Parkinson's disease
  申请人：H. Lundbeck A/S

  公开号：US10729710B2

  公开（公告）日：2020-08-04

  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); 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.

  本发明提供的式(I)化合物是儿茶酚胺的原药，可用于治疗神经退行性疾病和紊乱。本发明还提供了包含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失调的方法，特别是帕金森病。 因此，本发明涉及式（Id）化合物 式中 R1 为 H，R2 选自以下取代基（i）和（ii）之一；或 R1 选自以下取代基(i)和(ii)之一，R2 为 H；或 R1 和 R2 均由以下取代基(i)代表；或 R1 和 R2 均由以下取代基(ii)表示；或 R1 是取代基(i)，R2 是取代基(ii)；或 R1 为取代基(ii)，R2 为取代基(i)； 其中 * 表示连接点；以及 其中取代基 (i) 连接点上的碳原子为 S 构型； 或其药学上可接受的盐。
• CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE
  申请人：H. Lundbeck A/S

  公开号：US20190160083A1

  公开（公告）日：2019-05-30

  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); 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.
• NEW CATECHOLAMINE PRODRUGS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE
  申请人：H. Lundbeck A/S

  公开号：US20220257623A1

  公开（公告）日：2022-08-18

  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); 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.
• [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。