Prodrugs of opicapone

{
  "publication_number": "US2026103479A1",
  "country": "US",
  "kind": "A1",
  "title": "Prodrugs of opicapone",
  "abstract": "This invention relates to prodrugs of opicapone, their synthetic intermediates and pharmaceutically acceptable salts thereof. The invention also relates to methods of preparation of prodrugs of opicapone and pharmaceutically acceptable salts thereof. In particular, the invention relates to specific phosphate prodrugs of opicapone, pharmaceutically acceptable salts thereof and their synthetic intermediates, as well as methods of preparing the same. The invention also relates to administration routes for prodrugs of opicapone.",
  "claims": [
    "1. A compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein R is H or C 1 -C 6 alkyl and n is 0 or 1. 2. The compound according to claim 1, wherein the pharmaceutically acceptable salt is selected from the group consisting of a sodium salt, an ammonium salt and a potassium salt. 3. The compound according to claim 2, wherein the pharmaceutically acceptable salt is selected from the group consisting of a sodium salt and an ammonium salt. 4. The compound according to claim 3, wherein the sodium salt is a disodium salt and wherein the ammonium salt is a triammonium salt. 5. A method of preparing a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof, comprising: (a) deprotecting a compound of formula (II) so as to provide a compound of formula (I): wherein R 1 and R 2 are each independently a monovalent phosphate protecting group or together form a divalent phosphate protecting group; R is H or C 1 -C 6 alkyl and n is 0 or 1; and (b) optionally converting the compound of formula (I) to a pharmaceutically acceptable salt thereof. 6. The method of claim 5, wherein the phosphate protecting groups R 1 and R 2 are each independently selected from the group consisting of C 1 -C 6 alkyl and benzyl. 7. The method of claim 6, wherein the phosphate protecting groups R 1 and R 2 are both benzyl or both tert-butyl, or both ethyl. 8. The method of claim 5, wherein step (a) is carried out by reacting the compound of formula (II) with trimethylsilyl halide in an aprotic solvent, such as dichloromethane, or acetonitrile, followed by aqueous work up. 9. The method of claim 8, wherein the trimethylsilyl halide is trimethylsilyl bromide. 10. The method of claim 5, wherein the compound of formula (I) is converted to a pharmaceutically acceptable salt thereof. 11. The method of claim 10, wherein the pharmaceutically acceptable salt is selected from the group consisting of a sodium salt, an ammonium salt and a potassium salt. 12. The method of claim 11, wherein the pharmaceutically acceptable salt is selected from the group consisting of a sodium salt and an ammonium salt. 13. The method of claim 12, wherein the sodium salt is a disodium salt and wherein the ammonium salt is a triammonium salt. 14. A method of preparing a compound of formula (II), as defined in claim 5, comprising: reacting a compound of formula (III): with a compound of formula (IV): wherein R 1 and R 2 are each independently a monovalent phosphate protecting group or together form a divalent phosphate protecting group; R is H or C 1 -C 6 alkyl and n is 0 or 1; in the presence of a base and an aprotic solvent. 15. The method of claim 14, wherein the phosphate protecting groups R 1 and R 2 are each independently selected from the group consisting of C 1 -C 6 alkyl and benzyl. 16. (canceled) 17. (canceled) 18. A compound of formula (II): wherein R 1 and R 2 are each independently a monovalent phosphate protecting group or together form a divalent phosphate protecting group; R is H or C 1 -C 6 alkyl and n is 0 or 1. 19. (canceled) 20. (canceled) 21. A pharmaceutical formulation comprising: (i) a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients. 22. A pharmaceutical formulation for intravenous administration to a human being comprising: (i) a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof; and (ii) a pharmaceutically acceptable vehicle. 23. A pharmaceutical formulation for subcutaneous administration to a human being comprising: (i) a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof; and (ii) a pharmaceutically acceptable vehicle. 24. (canceled) 25. (canceled) 26. (canceled) 27. (canceled) 28. A method of treating Parkinson's disease, comprising administering the compound of claim 1, or a pharmaceutically acceptable salt thereof, to a patent in need thereof. 29. (canceled) 30. (canceled) 31. (canceled) 32. (canceled) 33. (canceled) 34. (canceled) 35. (canceled)"
  ],
  "cpc": [
    "C07F 9/65583",
    "A61K 31/675"
  ],
  "filing_date": "2023-03-31",
  "publication_date": "2026-04-16",
  "priority_date": "2022-04-01",
  "application_number": "US-202318852548-A"
}