NEW APORPHINE ESTERS AND THEIR USE IN THERAPY

• US 20080119504A1
• Filed: 01/29/2008
• Published: 05/22/2008
• Est. Priority Date: 08/17/2000
• Status: Abandoned Application

• Current Assignee: Axon Biochemicals BV
• Original Assignee: Axon Biochemicals BV
• Inventors: WIKSTROM, Hakan, Dijkstra, Durk, Jurva, Ulrik, Cremers, Thomas, Marchais, Sandrine, Andren, Per
• Application Number:
  US12/021,560
• Publication Number:
  US 20080119504A1
• Time in Patent Office: Days
• US Class Current: 514/284
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 5/12 for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
• CPC Class Codes: C07D 221/18 Ring systems of four or more rings
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

New aporphine derivatives are disclosed which have formula (I) and the physiologically acceptable salts thereof. Said derivatives may be used for the treatment of Parkinson'"'"'s disease, hemicrania, restless legs syndrome (RLS), sexual dysfunction in men and women, hyperprolactemia and psychotic disorders, and/or evaluation of Parkinson'"'"'s disease. Processes for the preparation of such derivates are also disclosed.

Claims

1. A method of treating sexual dysfunction in a subject in need thereof comprising administering a composition comprising a pharmaceutically acceptable carrier, diluent or excipient and an effective amount of an aporphine derivative of formula (I)

2. The method according to claim 1, wherein one of R₁ and R₂ is hydrogen or acetyl and the other one is selected from the group consisting of (C₃-C₂₀)alkanoyl, (C₄-C₇)cycloalkanoyl, benzoyl which is unsubstituted or substituted by a chlorine atom or 1 to 3 methoxy groups, phenylacetyl which may be substituted with a chlorine atom, and heteroarylacetyl, and R₃ is (C₁-C₃)alkyl or cyclopropyl.

3. The method according to claim 2, wherein one of R₁ and R₂ is hydrogen and the other one is selected from the group consisting of propanoyl, propenoyl, butanoyl, isobutanoyl, pivaloyl, decanoyl, hexadecanoyl, cyclopropanoyl and benzoyl and R₃ is methyl or propyl.

4. The method according to claim 2, wherein one of R₁ and R₂ is acetyl and the other one is selected from the group consisting of butanoyl, isobutanoyl, cyclopropanoyl, cyclohexanoyl, pivaloyl, decanoyl and hexadecanoyl and R₃ is methyl.

5. The method according to claim 1, wherein said composition is in the form of a patch or ointment for transdermal administration.

6. The method according to claim 5, wherein said composition further comprises one or more stabilizers, solubilizers and permeation activators to facilitate the passage of the active principle through the skin.

7. The method according to claim 1, wherein said composition is in the form of a depot preparation for subcutaneous or intramuscular administration comprising said aporphine derivative of formula I or the physiologically acceptable salt thereof dissolved or suspended in an oil.

8. The method according to claim 7, wherein said composition further comprises a local anesthetic.

9. The method according to claim 1, wherein said composition is in a form suited for oral, sublingual, pulmonary, rectal, vaginal or intraduodenal administration.

10. The method according to claim 1, wherein said composition further comprises an effective amount of an anti-emetic agent.

11. A method of treating sexual dysfunction in a subject in need thereof comprising administering a composition comprising a pharmaceutically acceptable carrier, diluent or excipient and an effective amount of an aporphine derivative of formula (I)

12. The method according to claim 11, wherein R₃ is (C₁-C₃)alkyl or cyclopropyl.

13. The method according to claim 12, wherein one of R₁ and R₂ is hydrogen and the other one is selected from the group consisting of propanoyl, propenoyl, butanoyl, isobutanoyl, pivaloyl, decanoyl, hexadecanoyl, cyclopropanoyl and benzoyl and R₃ is methyl or propyl.

14. The method according to claim 12, wherein one of R₁ and R₂ is hydrogen and the other one is selected from the group consisting of butanoyl, isobutanoyl, cyclopropanoyl, cyclohexanoyl, pivaloyl, decanoyl and hexadecanoyl and R₃ is methyl.

15. The method according to claim 12, wherein one of one of R₁ and R₂ is hydrogen and the other one is pivaloyl and R₃ is methyl.

16. The method according to claim 11, wherein said composition is in the form of a patch or ointment for transdermal administration.

17. The method according to claim 16, wherein said composition further comprises one or more stabilizers, solubilizers and permeation activators to facilitate the passage of the active principle through the skin.

18. The method according to claim 11, wherein said composition is in the form of a depot preparation for subcutaneous or intramuscular administration comprising said aporphine derivative of formula I or the physiologically acceptable salt thereof dissolved or suspended in an oil.

19. The method according to claim 18, wherein said composition further comprises a local anesthetic.

20. The method according to claim 11, wherein said composition is in a form suited for oral, sublingual, pulmonary, rectal, vaginal or intraduodenal administration.

21. The method according to claim 11, wherein said composition further comprises an effective amount of an anti-emetic agent.