Novel catecholamine prodrugs for use in the treatment of Parkinson's disease

Abstract

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 where treatment with a dopamine agonist is therapeutically beneficial, and pharmaceutical compositions comprising the compounds of the invention. Compounds according to the invention have the formula (Id), wherein R1 and R2 are each independently selected from H and the following substituent (iii), wherein: * indicates the point of attachment to the oxygen, and R3 is selected from H and COR4, and R4 is selected from H and C1-C6 alkyl, with the proviso that R1 and R2 cannot both be H, or a pharmaceutically acceptable salt thereof. [Formula 1] JPEG2023552699000031.jpg29170

Claims

1. The following formula (Id) 【Chemistry 1】 (In the formula, R1 and R2 are each independently H and the following substituents (iii) 【Chemistry 2】 (In the formula, ＊ This indicates the bonding point with oxygen, R3 is H. Selected from, (However, this is subject to the condition that neither R1 nor R2 can be H.) Compounds or pharmaceutically acceptable salts thereof.

2. The compounds are (4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-7-ylsulfamate of formula (II) and (4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6-ylsulfamate of formula (III). 【Transformation 3】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the above.

3. The compound is (4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-7-ylsulfamate of the following formula (II) 【Chemistry 4】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. The compound is (4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6-ylsulfamate of the following formula (III) 【Transformation 5】 The compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof.

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, in solid form.

6. A pharmaceutically acceptable salt of the compound according to any one of claims 1 to 5.

7. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, for use as a pharmaceutical.

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, and one or more pharmaceutically acceptable excipients.

9. The pharmaceutical composition according to claim 8, comprising a tablet or capsule for oral administration.

10. A pharmaceutical composition according to any one of claims 8 to 9, for use in the treatment of neurodegenerative diseases or disorders including Parkinson's disease, Huntington's disease, restless limb syndrome, or Alzheimer's disease; or neuropsychiatric disorders or disorders including schizophrenia, attention deficit hyperactivity disorder, or drug addiction.

11. The pharmaceutical composition according to claim 10 for use in the treatment of Parkinson's disease.

12. Use of a compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to any one of claims 8 to 9 in the manufacture of a pharmaceutical for the treatment of neurodegenerative diseases or disorders, including Parkinson's disease, Huntington's disease, restless limb syndrome, or Alzheimer's disease; or neuropsychiatric disorders or disorders, including schizophrenia, attention deficit hyperactivity disorder, or drug addiction.

13. The use according to claim 12, wherein the pharmaceutical product is for the treatment of Parkinson's disease.

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